CA2062094C - Methode de traitement des manies - Google Patents

Methode de traitement des manies

Info

Publication number: CA2062094C
Authority: CA; Canada
Prior art keywords: galanthamine; mania; substituted; acetylcholinesterase; hydrogen
Prior art date: 1991-05-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA 2062094

Other languages

English (en)

Other versions

CA2062094A1 (fr

Inventor

Ernir Snorrason

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-05-14

Filing date

1992-02-28

Publication date

1999-11-23

1991-05-14 Priority claimed from IS3706A external-priority patent/IS3706A7/is

1992-02-13 Priority claimed from DK18392A external-priority patent/DK18392D0/da

1992-02-28 Application filed by Individual filed Critical Individual

1992-11-15 Publication of CA2062094A1 publication Critical patent/CA2062094A1/fr

1999-11-23 Application granted granted Critical

1999-11-23 Publication of CA2062094C publication Critical patent/CA2062094C/fr

2012-02-28 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

206010026749 Mania Diseases 0.000 title claims abstract description 84
238000000034 method Methods 0.000 title claims description 14
ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims abstract description 142
229960003980 galantamine Drugs 0.000 claims abstract description 71
ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims abstract description 65
HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 claims abstract description 64
LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 claims abstract description 64
BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 claims abstract description 64
IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 claims abstract description 64
239000000544 cholinesterase inhibitor Substances 0.000 claims abstract description 29
229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims abstract description 18
150000003839 salts Chemical class 0.000 claims abstract description 13
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims abstract description 9
108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims abstract description 9
230000000694 effects Effects 0.000 claims description 48
238000011282 treatment Methods 0.000 claims description 46
108010022752 Acetylcholinesterase Proteins 0.000 claims description 26
102100033639 Acetylcholinesterase Human genes 0.000 claims description 26
229940022698 acetylcholinesterase Drugs 0.000 claims description 26
150000001875 compounds Chemical class 0.000 claims description 21
241000282412 Homo Species 0.000 claims description 20
230000008499 blood brain barrier function Effects 0.000 claims description 19
210000001218 blood-brain barrier Anatomy 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
108010053652 Butyrylcholinesterase Proteins 0.000 claims description 15
102100032404 Cholinesterase Human genes 0.000 claims description 15
230000005764 inhibitory process Effects 0.000 claims description 15
-1 nitro, amino Chemical group 0.000 claims description 15
125000004432 carbon atom Chemical group C* 0.000 claims description 12
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000003118 aryl group Chemical group 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 7
238000001727 in vivo Methods 0.000 claims description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
229960000890 hydrocortisone Drugs 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
210000003743 erythrocyte Anatomy 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
241000282414 Homo sapiens Species 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000001931 aliphatic group Chemical group 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000005037 alkyl phenyl group Chemical class 0.000 claims description 4
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 4
125000005161 aryl oxy carbonyl group Chemical class 0.000 claims description 4
125000005110 aryl thio group Chemical group 0.000 claims description 4
125000001231 benzoyloxy group Chemical class C(C1=CC=CC=C1)(=O)O* 0.000 claims description 4
125000000623 heterocyclic group Chemical class 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
229940122041 Cholinesterase inhibitor Drugs 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical class [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000002877 alkyl aryl group Chemical group 0.000 claims description 2
125000005248 alkyl aryloxy group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000004103 aminoalkyl group Chemical group 0.000 claims description 2
125000006196 aroyl alkyl group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000005358 mercaptoalkyl group Chemical group 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical class [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
229910052698 phosphorus Chemical class 0.000 claims description 2
239000011574 phosphorus Chemical class 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
150000007659 semicarbazones Chemical class 0.000 claims description 2
125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims 3
VLGAHTYYCHWLNI-BHRZLAGCSA-N 1w4l Chemical compound O1C(=C23)C(OC)=CC=C2C=[N+](CCCCCCCCN2C(C4=CC=CC=C4C2=O)=O)CC[C@]23[C@@H]1C[C@@H](O)C=C2 VLGAHTYYCHWLNI-BHRZLAGCSA-N 0.000 claims 2
238000007911 parenteral administration Methods 0.000 claims 2
125000003435 aroyl group Chemical group 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
229940079593 drug Drugs 0.000 description 25
239000003814 drug Substances 0.000 description 25
238000012360 testing method Methods 0.000 description 24
DITOENWBJBNZSL-UHFFFAOYSA-N O-methyl-hippeastrine Natural products C1=C2C3C4N(C)CCC4=CC(OC)C3OC(=O)C2=CC2=C1OCO2 DITOENWBJBNZSL-UHFFFAOYSA-N 0.000 description 18
QORVDGQLPPAFRS-XPSHAMGMSA-N galantamine hydrobromide Chemical compound Br.O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 QORVDGQLPPAFRS-XPSHAMGMSA-N 0.000 description 18
208000024891 symptom Diseases 0.000 description 14
210000004556 brain Anatomy 0.000 description 13
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 11
230000001505 hypomanic effect Effects 0.000 description 11
229910052744 lithium Inorganic materials 0.000 description 11
230000037396 body weight Effects 0.000 description 9
239000003176 neuroleptic agent Substances 0.000 description 9
210000000133 brain stem Anatomy 0.000 description 8
201000010099 disease Diseases 0.000 description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
235000013350 formula milk Nutrition 0.000 description 8
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208000019022 Mood disease Diseases 0.000 description 7
241000700159 Rattus Species 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
239000002775 capsule Substances 0.000 description 7
230000001713 cholinergic effect Effects 0.000 description 7
230000004044 response Effects 0.000 description 7
PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 6
230000000994 depressogenic effect Effects 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
229960001697 physostigmine Drugs 0.000 description 6
PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 6
208000017194 Affective disease Diseases 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
230000007958 sleep Effects 0.000 description 5
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239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 4
206010020751 Hypersensitivity Diseases 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
230000008859 change Effects 0.000 description 4
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 4
229960000258 corticotropin Drugs 0.000 description 4
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LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 4
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
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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
QDWJJTJNXAKQKD-UHFFFAOYSA-N trihexyphenidyl hydrochloride Chemical compound Cl.C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 QDWJJTJNXAKQKD-UHFFFAOYSA-N 0.000 description 2
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CA 2062094 1991-05-14 1992-02-28 Methode de traitement des manies Expired - Fee Related CA2062094C (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
IS3706		1991-05-14
IS3706A IS3706A7 (is)	1991-05-14	1991-05-14	Notkun á galantamine-hydróbrómíði í geðlæknisfræði
DK183/92		1992-02-13
DK18392A DK18392D0 (da)	1992-02-13	1992-02-13	Method of treating mania

Publications (2)

Publication Number	Publication Date
CA2062094A1 CA2062094A1 (fr)	1992-11-15
CA2062094C true CA2062094C (fr)	1999-11-23

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1992
- 1992-02-28 CA CA 2062094 patent/CA2062094C/fr not_active Expired - Fee Related

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CA2062094A1 (fr)	1992-11-15

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Date	Code	Title	Description
1995-03-31	EEER	Examination request
2011-02-28	MKLA	Lapsed

Publication	Publication Date	Title
US5336675A (en)	1994-08-09	Method of treating mania in humans
JP3291730B2 (ja)	2002-06-10	疲労症候群の治療
US4499096A (en)	1985-02-12	Rapid method for interrupting the narcotic addiction syndrome
US5026697A (en)	1991-06-25	Rapid method for interrupting or attenuating the nicotine/tobacco dependency syndrome
US5147872A (en)	1992-09-15	Treatment of immunologically based disorders, specifically psoriasis
KR970002246B1 (ko)	1997-02-26	뇌혈관 장해 치료용 약제조성물
US4670459A (en)	1987-06-02	Method of alleviating withdrawal symptoms
US7297691B2 (en)	2007-11-20	Treatment of sleep disorders with cholinesterase inhibitors
US4382946A (en)	1983-05-10	Method of alleviating withdrawal symptoms
US4946848A (en)	1990-08-07	Method of treating pruritus with nalmefene and clonidine
CA2062094C (fr)	1999-11-23	Methode de traitement des manies
Le Blaye et al.	1992	Acute ketotifen overdosage: a review of present clinical experience
CA2253473A1 (fr)	1997-11-13	Emploi de la pyridyl-piperazine et de la pyrimydil-piperazine pour le traitement de troubles lies a la toxicomanie
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JPH0259522A (ja)	1990-02-28	悩代謝及び／又は精神症状改善剤
Lowry et al.	1979	Controlled and noncontrolled but commonly abused substances
Sallan et al.	1975	TRēFried by permission. All rightsresēVēd.