IL154456A - S-alkylisothiouronium derivatives for the treatment of headache, migraine, nausea and vomiting - Google Patents
S-alkylisothiouronium derivatives for the treatment of headache, migraine, nausea and vomitingInfo
- Publication number
- IL154456A IL154456A IL154456A IL15445603A IL154456A IL 154456 A IL154456 A IL 154456A IL 154456 A IL154456 A IL 154456A IL 15445603 A IL15445603 A IL 15445603A IL 154456 A IL154456 A IL 154456A
- Authority
- IL
- Israel
- Prior art keywords
- migraine
- headache
- compound
- nausea
- ethylisothiouronium
- Prior art date
Links
- 208000019695 Migraine disease Diseases 0.000 title claims abstract description 153
- 206010019233 Headaches Diseases 0.000 title claims abstract description 84
- 231100000869 headache Toxicity 0.000 title claims abstract description 73
- 206010047700 Vomiting Diseases 0.000 title claims abstract description 43
- 206010027599 migraine Diseases 0.000 title claims description 147
- 206010028813 Nausea Diseases 0.000 title claims description 32
- 230000008693 nausea Effects 0.000 title claims description 32
- 238000011282 treatment Methods 0.000 claims abstract description 62
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 claims abstract description 49
- 239000003814 drug Substances 0.000 claims description 79
- 150000001875 compounds Chemical class 0.000 claims description 69
- 239000003826 tablet Substances 0.000 claims description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 239000002775 capsule Substances 0.000 claims description 21
- 230000003474 anti-emetic effect Effects 0.000 claims description 12
- 230000002460 anti-migrenic effect Effects 0.000 claims description 11
- 230000008673 vomiting Effects 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000001062 anti-nausea Effects 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- NXHQGHMUIRHPLZ-UHFFFAOYSA-N CC(C)COP(O)O.CC(C)CSC(N)=N.CC(C)CSC(N)=N Chemical compound CC(C)COP(O)O.CC(C)CSC(N)=N.CC(C)CSC(N)=N NXHQGHMUIRHPLZ-UHFFFAOYSA-N 0.000 claims description 4
- UJRHNBBBWMFTKQ-UHFFFAOYSA-N CC(C)OP(O)O.CC(C)SC(N)=N.CC(C)SC(N)=N Chemical compound CC(C)OP(O)O.CC(C)SC(N)=N.CC(C)SC(N)=N UJRHNBBBWMFTKQ-UHFFFAOYSA-N 0.000 claims description 4
- CYYJBBMXGOJTIQ-UHFFFAOYSA-N CCCOP(O)O.CCCSC(N)=N.CCCSC(N)=N Chemical compound CCCOP(O)O.CCCSC(N)=N.CCCSC(N)=N CYYJBBMXGOJTIQ-UHFFFAOYSA-N 0.000 claims description 4
- OSBXGLCAOCDMAR-UHFFFAOYSA-N COP(O)O.CSC(N)=N.CSC(N)=N Chemical compound COP(O)O.CSC(N)=N.CSC(N)=N OSBXGLCAOCDMAR-UHFFFAOYSA-N 0.000 claims description 4
- SUDLUXBNOZCRIJ-UHFFFAOYSA-N [amino(butylsulfanyl)methylidene]azanium;dibutyl phosphate Chemical compound CCCCSC(N)=N.CCCCOP(O)(=O)OCCCC SUDLUXBNOZCRIJ-UHFFFAOYSA-N 0.000 claims description 4
- YFEHFLUEQSONBX-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]azanium;dimethyl phosphate Chemical compound CSC(N)=N.COP(O)(=O)OC YFEHFLUEQSONBX-UHFFFAOYSA-N 0.000 claims description 4
- XSXAFBUBMLOYIX-UHFFFAOYSA-N ethyl carbamimidothioate ethyl dihydrogen phosphite Chemical compound CCOP(O)O.CCSC(N)=N.CCSC(N)=N XSXAFBUBMLOYIX-UHFFFAOYSA-N 0.000 claims description 4
- 238000004806 packaging method and process Methods 0.000 claims description 2
- 239000003708 ampul Substances 0.000 claims 2
- 208000024891 symptom Diseases 0.000 abstract description 35
- 239000000203 mixture Substances 0.000 abstract description 19
- 206010034960 Photophobia Diseases 0.000 abstract description 8
- 230000002265 prevention Effects 0.000 abstract description 6
- 238000002512 chemotherapy Methods 0.000 abstract description 5
- 206010054956 Phonophobia Diseases 0.000 abstract description 3
- 238000001959 radiotherapy Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 description 52
- -1 painkillers Substances 0.000 description 38
- 230000000694 effects Effects 0.000 description 35
- 208000002193 Pain Diseases 0.000 description 25
- 230000036407 pain Effects 0.000 description 25
- 150000001450 anions Chemical class 0.000 description 20
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 239000002111 antiemetic agent Substances 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 14
- 229910052736 halogen Inorganic materials 0.000 description 13
- 230000009467 reduction Effects 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 229940125683 antiemetic agent Drugs 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 8
- 206010015037 epilepsy Diseases 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 229940125684 antimigraine agent Drugs 0.000 description 7
- 239000002282 antimigraine agent Substances 0.000 description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 7
- 229960004316 cisplatin Drugs 0.000 description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000001188 haloalkyl group Chemical group 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 108010010803 Gelatin Proteins 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 125000005248 alkyl aryloxy group Chemical group 0.000 description 6
- 150000008051 alkyl sulfates Chemical class 0.000 description 6
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 6
- 125000005362 aryl sulfone group Chemical group 0.000 description 6
- 125000005361 aryl sulfoxide group Chemical group 0.000 description 6
- 125000004104 aryloxy group Chemical group 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 239000008273 gelatin Substances 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- CTYRPMDGLDAWRQ-UHFFFAOYSA-N phenyl hydrogen sulfate Chemical compound OS(=O)(=O)OC1=CC=CC=C1 CTYRPMDGLDAWRQ-UHFFFAOYSA-N 0.000 description 6
- 150000003138 primary alcohols Chemical group 0.000 description 6
- 150000003141 primary amines Chemical group 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 150000003333 secondary alcohols Chemical group 0.000 description 6
- 150000003335 secondary amines Chemical group 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 229940124530 sulfonamide Drugs 0.000 description 6
- 150000003456 sulfonamides Chemical class 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 125000004001 thioalkyl group Chemical group 0.000 description 6
- 208000001953 Hypotension Diseases 0.000 description 5
- 241000282339 Mustela Species 0.000 description 5
- 229940035676 analgesics Drugs 0.000 description 5
- 239000000730 antalgic agent Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 206010019133 Hangover Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010027603 Migraine headaches Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 206010036618 Premenstrual syndrome Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 229960004943 ergotamine Drugs 0.000 description 4
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 4
- 231100000957 no side effect Toxicity 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 208000035824 paresthesia Diseases 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 231100000111 LD50 Toxicity 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000000060 Migraine with aura Diseases 0.000 description 3
- 206010047139 Vasoconstriction Diseases 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 230000004438 eyesight Effects 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 206010052787 migraine without aura Diseases 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000035807 sensation Effects 0.000 description 3
- 235000019615 sensations Nutrition 0.000 description 3
- 239000000952 serotonin receptor agonist Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 229960003708 sumatriptan Drugs 0.000 description 3
- 150000003509 tertiary alcohols Chemical group 0.000 description 3
- 150000003512 tertiary amines Chemical group 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000006561 Cluster Headache Diseases 0.000 description 2
- 206010015124 Ergot poisoning Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 description 2
- 208000005374 Poisoning Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000001431 Psychomotor Agitation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 206010047141 Vasodilatation Diseases 0.000 description 2
- 206010047571 Visual impairment Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 208000011861 acute hypotension Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229940124433 antimigraine drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 150000003936 benzamides Chemical class 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 230000001667 episodic effect Effects 0.000 description 2
- 208000006852 ergotism Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000005555 hypertensive agent Substances 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 229960004503 metoclopramide Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000013465 muscle pain Diseases 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 210000004916 vomit Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 description 1
- 102100027493 5-hydroxytryptamine receptor 1D Human genes 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010001540 Akathisia Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- 206010008531 Chills Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 206010056465 Food craving Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010058490 Hyperoxia Diseases 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027940 Mood altered Diseases 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 206010034568 Peripheral coldness Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241001282135 Poromitra oscitans Species 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 206010039729 Scotoma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 206010048232 Yawning Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000002959 anti-hypotensive effect Effects 0.000 description 1
- 229940124572 antihypotensive agent Drugs 0.000 description 1
- 229940005486 antimigraine preparations Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- AMLYRCOEFHJSFS-UHFFFAOYSA-N carbazol-1-one Chemical class C1=CC=C2C3=CC=CC(=O)C3=NC2=C1 AMLYRCOEFHJSFS-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000002895 emetic Substances 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- 125000006232 ethoxy propyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000000222 hyperoxic effect Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229940090436 imitrex Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000036540 impulse transmission Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004914 menses Anatomy 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960001186 methysergide Drugs 0.000 description 1
- 230000007510 mood change Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960003940 naproxen sodium Drugs 0.000 description 1
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 229940084026 sodium valproate Drugs 0.000 description 1
- YHKQUERNJBHAGZ-RWHAEUCFSA-M sodium;(4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1-[(4-tert-butylphenyl)methyl]-4-[(4-chlorophenyl)-phenylmethyl]piperazine;n-(4-hyd Chemical compound [Na+].Cl.Cl.OP(O)(O)=O.CC(=O)NC1=CC=C(O)C=C1.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC.C1=CC(C(C)(C)C)=CC=C1CN1CCN(C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1 YHKQUERNJBHAGZ-RWHAEUCFSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229960000658 sumatriptan succinate Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- ULSDMUVEXKOYBU-ZDUSSCGKSA-N zolmitriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C[C@H]1COC(=O)N1 ULSDMUVEXKOYBU-ZDUSSCGKSA-N 0.000 description 1
- 229940003675 zomig Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Plant Substances (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL154456A IL154456A (en) | 2000-09-05 | 2003-02-13 | S-alkylisothiouronium derivatives for the treatment of headache, migraine, nausea and vomiting |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22981200P | 2000-09-05 | 2000-09-05 | |
| IL14463201A IL144632A0 (en) | 2001-07-30 | 2001-07-30 | Method and pharmaceutical compositions for treating headache, nausea and migraine |
| PCT/IL2001/000817 WO2002019961A2 (en) | 2000-09-05 | 2001-08-30 | Pharmaceutical compositions for headache, migraine, nausea and emesis |
| IL154456A IL154456A (en) | 2000-09-05 | 2003-02-13 | S-alkylisothiouronium derivatives for the treatment of headache, migraine, nausea and vomiting |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL154456A true IL154456A (en) | 2013-05-30 |
Family
ID=26324036
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL154456A IL154456A (en) | 2000-09-05 | 2003-02-13 | S-alkylisothiouronium derivatives for the treatment of headache, migraine, nausea and vomiting |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US7148208B2 (de) |
| EP (1) | EP1315505B1 (de) |
| JP (1) | JP2004508311A (de) |
| KR (1) | KR100849999B1 (de) |
| CN (1) | CN100448439C (de) |
| AT (1) | ATE375797T1 (de) |
| AU (2) | AU8617801A (de) |
| BR (1) | BR0113698A (de) |
| CA (1) | CA2420410C (de) |
| CY (1) | CY1107270T1 (de) |
| DE (1) | DE60131004T2 (de) |
| DK (1) | DK1315505T3 (de) |
| ES (1) | ES2296792T3 (de) |
| HU (1) | HUP0302362A3 (de) |
| IL (1) | IL154456A (de) |
| MD (1) | MD2447G2 (de) |
| MX (1) | MXPA03001737A (de) |
| NO (1) | NO20031902L (de) |
| NZ (1) | NZ524903A (de) |
| PT (1) | PT1315505E (de) |
| WO (1) | WO2002019961A2 (de) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2420410C (en) * | 2000-09-05 | 2011-04-26 | Meditor Pharmaceuticals Ltd. | Pharmaceutical compositions for headache, migraine, nausea and emesis |
| US20090186854A1 (en) * | 2006-03-23 | 2009-07-23 | Meditor Pharmaceuticals Ltd. | S-alkylisothiouronium derivatives for the treatment of inflammatory diseases |
| EP2167050A1 (de) * | 2007-06-13 | 2010-03-31 | Meditor Pharmaceuticals Ltd. | Geschmacksmaskierte pharmazeutische zusammensetzungen von s-alkylisothiouronium-derivaten |
| RU2342923C1 (ru) * | 2007-07-26 | 2009-01-10 | Общество с ограниченной ответственностью "Бентус лаборатории" | Дезинфицирующее антисептическое средство для обработки рук с увлажняющим эффектом (варианты) |
| MD3619G2 (ro) * | 2007-11-06 | 2009-01-31 | Рафаэль Баркан | Remediu medicamentos nazal cu acţiune anticongestivă |
| US12011423B2 (en) | 2007-11-06 | 2024-06-18 | Foraviset Ltd. | S-alkylisothiouronium derivatives for treating uterine hypercontractility disorders |
| EA030035B1 (ru) * | 2007-11-06 | 2018-06-29 | Меламед, Лемуил | Применение s-этилизотиоурония диэтилфосфата для изготовления лекарственного средства для лечения нарушения матки |
| US8615407B2 (en) | 2008-04-24 | 2013-12-24 | The Invention Science Fund I, Llc | Methods and systems for detecting a bioactive agent effect |
| US7974787B2 (en) * | 2008-04-24 | 2011-07-05 | The Invention Science Fund I, Llc | Combination treatment alteration methods and systems |
| US9064036B2 (en) | 2008-04-24 | 2015-06-23 | The Invention Science Fund I, Llc | Methods and systems for monitoring bioactive agent use |
| US20100063368A1 (en) * | 2008-04-24 | 2010-03-11 | Searete Llc, A Limited Liability Corporation | Computational system and method for memory modification |
| US8682687B2 (en) | 2008-04-24 | 2014-03-25 | The Invention Science Fund I, Llc | Methods and systems for presenting a combination treatment |
| US8876688B2 (en) | 2008-04-24 | 2014-11-04 | The Invention Science Fund I, Llc | Combination treatment modification methods and systems |
| US9662391B2 (en) | 2008-04-24 | 2017-05-30 | The Invention Science Fund I Llc | Side effect ameliorating combination therapeutic products and systems |
| US9649469B2 (en) | 2008-04-24 | 2017-05-16 | The Invention Science Fund I Llc | Methods and systems for presenting a combination treatment |
| US9560967B2 (en) | 2008-04-24 | 2017-02-07 | The Invention Science Fund I Llc | Systems and apparatus for measuring a bioactive agent effect |
| US9239906B2 (en) | 2008-04-24 | 2016-01-19 | The Invention Science Fund I, Llc | Combination treatment selection methods and systems |
| US20100069724A1 (en) * | 2008-04-24 | 2010-03-18 | Searete Llc | Computational system and method for memory modification |
| US9449150B2 (en) | 2008-04-24 | 2016-09-20 | The Invention Science Fund I, Llc | Combination treatment selection methods and systems |
| US9282927B2 (en) | 2008-04-24 | 2016-03-15 | Invention Science Fund I, Llc | Methods and systems for modifying bioactive agent use |
| US20100130811A1 (en) * | 2008-04-24 | 2010-05-27 | Searete Llc | Computational system and method for memory modification |
| US9026369B2 (en) | 2008-04-24 | 2015-05-05 | The Invention Science Fund I, Llc | Methods and systems for presenting a combination treatment |
| US8606592B2 (en) | 2008-04-24 | 2013-12-10 | The Invention Science Fund I, Llc | Methods and systems for monitoring bioactive agent use |
| US20090270687A1 (en) * | 2008-04-24 | 2009-10-29 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Methods and systems for modifying bioactive agent use |
| US8930208B2 (en) | 2008-04-24 | 2015-01-06 | The Invention Science Fund I, Llc | Methods and systems for detecting a bioactive agent effect |
| US8357117B2 (en) * | 2008-08-06 | 2013-01-22 | Family Health International | Device and method for delivering an agent into breast milk while breastfeeding |
| WO2012018341A1 (en) * | 2010-08-05 | 2012-02-09 | Family Health International | Device and method for delivering an agent into breast milk while breastfeeding |
| CN109523244B (zh) * | 2018-11-02 | 2023-06-27 | 创新先进技术有限公司 | 一种基于母子账户的用于转移款项数据的方法和系统 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2419675A1 (fr) * | 1978-03-16 | 1979-10-12 | Philagro Sa | Compositions fongicides a base de phosphites d'isothiouronium |
| GB9418912D0 (en) * | 1994-09-20 | 1994-11-09 | Fisons Corp | Pharmaceutically active compounds |
| MD263C2 (ro) * | 1995-03-01 | 1995-12-31 | Виктор ГИКАВЫЙ | Remediu cu acţiune antihipotensivă "IZOTURON" |
| MD586C2 (ro) * | 1995-05-25 | 1997-03-31 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Substanţă medicamentoasă cu acţiune antihipotensivă "Difetur" |
| FR2753098B1 (fr) * | 1996-09-06 | 1998-11-27 | Sod Conseils Rech Applic | Composition pharmaceutique comprenant au moins un inhibiteur de no synthase et au moins un piegeur des formes reactives de l'oxygene |
| WO1998013036A1 (en) * | 1996-09-26 | 1998-04-02 | Meditor Pharmaceuticals Ltd. | Pharmaceutical compositions comprising s-alkylisothiouronium derivatives |
| EP1829539A3 (de) * | 1996-11-05 | 2008-02-20 | HEADEXPLORER ApS | Methoden zur Behandlung von anspannungsbedingten Kopfschmerzen |
| MD1138C2 (ro) * | 1997-02-17 | 1999-07-31 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Izopropilfosfit-S-izopropilizotiuroniu- substanţă cu acţiune hipertensivă |
| MD1223C2 (ro) * | 1997-07-15 | 2000-01-31 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Aplicarea dimetilfosfatului de S-metil-izo-tiouroniu în calitate de substanţă vasoconstrictoare şi preparat farmaceutic pe baza lui |
| US6127420A (en) * | 1997-08-22 | 2000-10-03 | The Medical College Of Wisconsin Research Foundation, Inc. | L-N5 -(1-imino-3-alkenyl) ornithine and related compounds and use thereof |
| MD1431G2 (ro) * | 1998-01-16 | 2001-02-28 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Remedii antihipotensive |
| US6093743A (en) * | 1998-06-23 | 2000-07-25 | Medinox Inc. | Therapeutic methods employing disulfide derivatives of dithiocarbamates and compositions useful therefor |
| FR2788771B1 (fr) | 1999-01-22 | 2001-04-13 | Pf Medicament | Nouvelles 1,2-alcoyl-1-[1-[aryl (alcoyl) oxyalcoyl] piperidin-4-yl]-3-aryl isothiourees substituees, leur preparation et leur application en therapeutique |
| AU3511500A (en) * | 1999-03-05 | 2000-09-21 | Trustees Of University Technology Corporation, The | Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide-induced clinical conditions |
| JP2003505427A (ja) * | 1999-07-21 | 2003-02-12 | オメロス コーポレイション | 疼痛、炎症および軟骨分解の抑制のための溶液および方法 |
| CA2420410C (en) * | 2000-09-05 | 2011-04-26 | Meditor Pharmaceuticals Ltd. | Pharmaceutical compositions for headache, migraine, nausea and emesis |
-
2001
- 2001-08-30 CA CA2420410A patent/CA2420410C/en not_active Expired - Fee Related
- 2001-08-30 AU AU8617801A patent/AU8617801A/xx active Pending
- 2001-08-30 AU AU2001286178A patent/AU2001286178B2/en not_active Ceased
- 2001-08-30 NZ NZ524903A patent/NZ524903A/en not_active IP Right Cessation
- 2001-08-30 PT PT01965546T patent/PT1315505E/pt unknown
- 2001-08-30 DE DE60131004T patent/DE60131004T2/de not_active Expired - Lifetime
- 2001-08-30 BR BR0113698-4A patent/BR0113698A/pt not_active Application Discontinuation
- 2001-08-30 JP JP2002524446A patent/JP2004508311A/ja active Pending
- 2001-08-30 WO PCT/IL2001/000817 patent/WO2002019961A2/en not_active Ceased
- 2001-08-30 AT AT01965546T patent/ATE375797T1/de active
- 2001-08-30 HU HU0302362A patent/HUP0302362A3/hu unknown
- 2001-08-30 CN CNB018151795A patent/CN100448439C/zh not_active Expired - Fee Related
- 2001-08-30 DK DK01965546T patent/DK1315505T3/da active
- 2001-08-30 MX MXPA03001737A patent/MXPA03001737A/es active IP Right Grant
- 2001-08-30 MD MDA20020139A patent/MD2447G2/ro not_active IP Right Cessation
- 2001-08-30 EP EP01965546A patent/EP1315505B1/de not_active Expired - Lifetime
- 2001-08-30 ES ES01965546T patent/ES2296792T3/es not_active Expired - Lifetime
- 2001-08-30 KR KR1020037003277A patent/KR100849999B1/ko not_active Expired - Fee Related
-
2003
- 2003-02-13 IL IL154456A patent/IL154456A/en not_active IP Right Cessation
- 2003-03-05 US US10/382,217 patent/US7148208B2/en not_active Expired - Lifetime
- 2003-04-28 NO NO20031902A patent/NO20031902L/no not_active Application Discontinuation
-
2006
- 2006-10-18 US US11/550,548 patent/US8673979B2/en not_active Expired - Fee Related
-
2008
- 2008-01-17 CY CY20081100071T patent/CY1107270T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2420410C (en) | Pharmaceutical compositions for headache, migraine, nausea and emesis | |
| AU2001286178A1 (en) | Pharmaceutical compositions for headache, migraine, nausea and emesis | |
| MERHOFF et al. | Ergot intoxication: historical review and description of unusual clinical manifestations | |
| CA2260943C (en) | Formulation of 5-ht agonists | |
| KR20090021169A (ko) | Ｒ(+) 및 ｓ(-) 프라미펙솔을 포함하는 조성물 및 이의 사용 방법 | |
| US4804669A (en) | Treatment of pain with a piperidine | |
| CA1157379A (en) | Method of preparation of pharmaceutical composition for treating peripheral orthostatic hypotention | |
| NZ506020A (en) | Use of pharmaceutical combinations containing tramadol and an antiemetic | |
| KR100367791B1 (ko) | 테트라하이드로벤즈[ｃｄ]인돌-6-카복스아미드를 포함하는구토 예방용 약제 | |
| US4481206A (en) | Spiro succinimide derivative in the treatment of dementia of the Alzheimer type | |
| IE61612B1 (en) | Antiparkinson ergoline derivatives | |
| CN101448502A (zh) | 用于治疗慢性疼痛的特麦角脲/丙麦角脲 | |
| CA2066834A1 (en) | Use of glycine/nmda receptor ligands for the treatment of drug dependence and withdrawal | |
| KR100692235B1 (ko) | 안지오텐신 ⅱ 길항물질의 신규한 용도 | |
| US3644643A (en) | Method of reducing intraocular pressure using glycine | |
| JP4864259B2 (ja) | 性機能障害および血管収縮に関する疾患の予防および治療におけるイカリンの使用 | |
| RU2275905C2 (ru) | Фармацевтические композиции от головной боли, мигрени, тошноты и рвоты | |
| US4687771A (en) | Method for treatment of male impotence | |
| NZ207411A (en) | Pharmaceutical compositions containing paracetamol and tizanidine | |
| Blackwell et al. | Antidepressant drugs | |
| JPS63132834A (ja) | 鎮静剤製剤 | |
| EP0342211B1 (de) | Behandlung von arteriosklerosis durch verabreichung von l-tryptophane oder l-5-hydroxytryptophan | |
| UA28717U (en) | Method for preventing or alleviating nausea or vomiting | |
| GB2135884A (en) | Analgesic preparations containing tizanidine and paracetamol | |
| KR20000029647A (ko) | 양극성장애의치료방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |