ZA200103236B - Treatment of disorders of the outer retina. - Google Patents

Treatment of disorders of the outer retina. Download PDF

Info

Publication number: ZA200103236B
Authority: ZA; South Africa
Prior art keywords: eliprodil; retinal; compound; alkyl; halogen
Prior art date: 1998-10-27

Application number

ZA200103236A

Other languages

English (en)

Inventor

Jr Robert J Collier

Mark R Hellberg

Michael A Kapin

George E Barnes

Michael L Chandler

Original Assignee

Alcon Lab Inc

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.)

1998-10-27

Filing date

2001-04-20

Publication date

2001-10-23

2001-04-20 Application filed by Alcon Lab Inc filed Critical Alcon Lab Inc

2001-10-23 Publication of ZA200103236B publication Critical patent/ZA200103236B/en

Links

210000001525 retina Anatomy 0.000 title claims description 42
238000011282 treatment Methods 0.000 title claims description 6
229950005455 eliprodil Drugs 0.000 claims description 45
GGUSQTSTQSHJAH-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-UHFFFAOYSA-N 0.000 claims description 44
150000001875 compounds Chemical class 0.000 claims description 33
230000002207 retinal effect Effects 0.000 claims description 27
239000000203 mixture Substances 0.000 claims description 21
229940122459 Glutamate antagonist Drugs 0.000 claims description 20
208000017442 Retinal disease Diseases 0.000 claims description 20
230000006378 damage Effects 0.000 claims description 20
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
206010038923 Retinopathy Diseases 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
208000035475 disorder Diseases 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 11
239000003825 glutamate receptor antagonist Substances 0.000 claims description 11
208000007014 Retinitis pigmentosa Diseases 0.000 claims description 10
208000014674 injury Diseases 0.000 claims description 10
125000004423 acyloxy group Chemical group 0.000 claims description 8
239000005557 antagonist Substances 0.000 claims description 8
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 8
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
208000002780 macular degeneration Diseases 0.000 claims description 8
229920000768 polyamine Polymers 0.000 claims description 8
206010038848 Retinal detachment Diseases 0.000 claims description 7
208000028867 ischemia Diseases 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
208000002367 Retinal Perforations Diseases 0.000 claims description 6
206010064930 age-related macular degeneration Diseases 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
230000000642 iatrogenic effect Effects 0.000 claims description 6
238000002647 laser therapy Methods 0.000 claims description 6
238000002428 photodynamic therapy Methods 0.000 claims description 6
238000004321 preservation Methods 0.000 claims description 6
230000004264 retinal detachment Effects 0.000 claims description 6
238000001356 surgical procedure Methods 0.000 claims description 6
230000008733 trauma Effects 0.000 claims description 6
208000001351 Epiretinal Membrane Diseases 0.000 claims description 5
230000005945 translocation Effects 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
238000000034 method Methods 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims 3
125000003545 alkoxy group Chemical group 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
241000700159 Rattus Species 0.000 description 47
239000003981 vehicle Substances 0.000 description 22
230000004044 response Effects 0.000 description 21
230000003902 lesion Effects 0.000 description 17
230000006870 function Effects 0.000 description 14
239000003194 amino acid receptor blocking agent Substances 0.000 description 11
238000009472 formulation Methods 0.000 description 10
QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 9
GGUSQTSTQSHJAH-FQEVSTJZSA-N (R)-eliprodil Chemical compound C([C@H](O)C=1C=CC(Cl)=CC=1)N(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-FQEVSTJZSA-N 0.000 description 8
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 8
210000004027 cell Anatomy 0.000 description 8
230000000694 effects Effects 0.000 description 8
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical class CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 7
201000007737 Retinal degeneration Diseases 0.000 description 7
108091008695 photoreceptors Proteins 0.000 description 7
238000011084 recovery Methods 0.000 description 7
230000004258 retinal degeneration Effects 0.000 description 7
230000000007 visual effect Effects 0.000 description 7
GGUSQTSTQSHJAH-HXUWFJFHSA-N (S)-eliprodil Chemical compound C([C@@H](O)C=1C=CC(Cl)=CC=1)N(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-HXUWFJFHSA-N 0.000 description 6
102000014649 NMDA glutamate receptor activity proteins Human genes 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
229940127291 Calcium channel antagonist Drugs 0.000 description 5
206010057430 Retinal injury Diseases 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 5
229960004640 memantine Drugs 0.000 description 5
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
208000005590 Choroidal Neovascularization Diseases 0.000 description 4
208000027418 Wounds and injury Diseases 0.000 description 4
230000006907 apoptotic process Effects 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000012458 free base Substances 0.000 description 4
208000015122 neurodegenerative disease Diseases 0.000 description 4
230000008832 photodamage Effects 0.000 description 4
210000000608 photoreceptor cell Anatomy 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
230000004243 retinal function Effects 0.000 description 4
230000035882 stress Effects 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
230000000699 topical effect Effects 0.000 description 4
UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 3
230000030833 cell death Effects 0.000 description 3
GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
230000007613 environmental effect Effects 0.000 description 3
239000003257 excitatory amino acid Substances 0.000 description 3
230000002461 excitatory amino acid Effects 0.000 description 3
SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 3
229960000326 flunarizine Drugs 0.000 description 3
229960003998 ifenprodil Drugs 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
230000000508 neurotrophic effect Effects 0.000 description 3
239000002997 ophthalmic solution Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
230000002265 prevention Effects 0.000 description 3
230000005855 radiation Effects 0.000 description 3
238000011160 research Methods 0.000 description 3
210000003583 retinal pigment epithelium Anatomy 0.000 description 3
QEMSVZNTSXPFJA-HNAYVOBHSA-N 1-[(1s,2s)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-4-phenylpiperidin-4-ol Chemical compound C1([C@H](O)[C@H](C)N2CCC(O)(CC2)C=2C=CC=CC=2)=CC=C(O)C=C1 QEMSVZNTSXPFJA-HNAYVOBHSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
108091006146 Channels Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
241000288906 Primates Species 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
238000010171 animal model Methods 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
229940072107 ascorbate Drugs 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
235000010323 ascorbic acid Nutrition 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000000480 calcium channel blocker Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
230000007850 degeneration Effects 0.000 description 2
230000003412 degenerative effect Effects 0.000 description 2
238000002571 electroretinography Methods 0.000 description 2
239000003623 enhancer Substances 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
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 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000013010 irrigating solution Substances 0.000 description 2
238000013532 laser treatment Methods 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
229940054534 ophthalmic solution Drugs 0.000 description 2
230000000649 photocoagulation Effects 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
230000009467 reduction Effects 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
239000000243 solution Substances 0.000 description 2
-1 such as Substances 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
230000004393 visual impairment Effects 0.000 description 2
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
FJLRGFADCXTJNV-CAWMZFRYSA-N (1s)-1-(2,3-dihydro-1-benzothiophen-5-yl)-2-(4-phenylbutylamino)propan-1-ol Chemical compound CC([C@@H](O)C=1C=C2CCSC2=CC=1)NCCCCC1=CC=CC=C1 FJLRGFADCXTJNV-CAWMZFRYSA-N 0.000 description 1
SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
ZBIAKUMOEKILTF-UHFFFAOYSA-N 2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-N-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 ZBIAKUMOEKILTF-UHFFFAOYSA-N 0.000 description 1
UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
201000004569 Blindness Diseases 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
206010060823 Choroidal neovascularisation Diseases 0.000 description 1
108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 1
108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
206010012689 Diabetic retinopathy Diseases 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
241000282414 Homo sapiens Species 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 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
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
241000282560 Macaca mulatta Species 0.000 description 1
208000035719 Maculopathy Diseases 0.000 description 1
FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
VLCDUOXHFNUCKK-UHFFFAOYSA-N N,N'-Dimethylthiourea Chemical compound CNC(=S)NC VLCDUOXHFNUCKK-UHFFFAOYSA-N 0.000 description 1
UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
108010025020 Nerve Growth Factor Proteins 0.000 description 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
208000037273 Pathologic Processes Diseases 0.000 description 1
IFFPICMESYHZPQ-UHFFFAOYSA-N Prenylamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CCNC(C)CC1=CC=CC=C1 IFFPICMESYHZPQ-UHFFFAOYSA-N 0.000 description 1
208000007135 Retinal Neovascularization Diseases 0.000 description 1
108010038912 Retinoid X Receptors Proteins 0.000 description 1
206010038933 Retinopathy of prematurity Diseases 0.000 description 1
241000555745 Sciuridae Species 0.000 description 1
229940123268 Sodium antagonist Drugs 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
206010053615 Thermal burn Diseases 0.000 description 1
229930003427 Vitamin E Chemical class 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
229960002576 amiloride Drugs 0.000 description 1
238000000540 analysis of variance Methods 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
210000002565 arteriole Anatomy 0.000 description 1
229960002992 barnidipine Drugs 0.000 description 1
VXMOONUMYLCFJD-DHLKQENFSA-N barnidipine Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@@H]2CN(CC=3C=CC=CC=3)CC2)=CC=CC([N+]([O-])=O)=C1 VXMOONUMYLCFJD-DHLKQENFSA-N 0.000 description 1
239000002585 base Substances 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
230000008499 blood brain barrier function Effects 0.000 description 1
229940082649 blood substitutes and perfusion irrigating solutions Drugs 0.000 description 1
210000001218 blood-brain barrier Anatomy 0.000 description 1
210000001775 bruch membrane Anatomy 0.000 description 1
239000000872 buffer Substances 0.000 description 1
230000005779 cell damage Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
210000003161 choroid Anatomy 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000001120 cytoprotective effect Effects 0.000 description 1
229960000958 deferoxamine Drugs 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960001985 dextromethorphan Drugs 0.000 description 1
229940061607 dibasic sodium phosphate Drugs 0.000 description 1
201000010099 disease Diseases 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
230000000763 evoking effect Effects 0.000 description 1
230000005284 excitation Effects 0.000 description 1
239000000928 excitatory amino acid agonist Substances 0.000 description 1
230000003492 excitotoxic effect Effects 0.000 description 1
231100000063 excitotoxicity Toxicity 0.000 description 1
239000003885 eye ointment Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Chemical class CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
238000010191 image analysis Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
235000019388 lanolin Nutrition 0.000 description 1
229960001941 lidoflazine Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000002502 liposome Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000011670 long-evans rat Methods 0.000 description 1
230000007774 longterm Effects 0.000 description 1
235000001055 magnesium Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
238000005259 measurement Methods 0.000 description 1
210000004379 membrane Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
229960004584 methylprednisolone Drugs 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
230000002438 mitochondrial effect Effects 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
230000004660 morphological change Effects 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
210000004126 nerve fiber Anatomy 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
230000000324 neuroprotective effect Effects 0.000 description 1
229960001783 nicardipine Drugs 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
229960000715 nimodipine Drugs 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
230000008397 ocular pathology Effects 0.000 description 1
229940100655 ophthalmic gel Drugs 0.000 description 1
229940069265 ophthalmic ointment Drugs 0.000 description 1
230000036542 oxidative stress Effects 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000009054 pathological process Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
238000005502 peroxidation Methods 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000000049 pigment Substances 0.000 description 1
230000019612 pigmentation Effects 0.000 description 1
239000000088 plastic resin Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229940094472 prenylamine lactate Drugs 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000003642 reactive oxygen metabolite Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
230000008439 repair process Effects 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
230000004281 retinal morphology Effects 0.000 description 1
239000000790 retinal pigment Substances 0.000 description 1
210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
230000003289 retinoprotective effect Effects 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
230000009834 selective interaction Effects 0.000 description 1
238000004904 shortening Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
241000894007 species Species 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
230000008961 swelling Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229940037128 systemic glucocorticoids Drugs 0.000 description 1
238000012353 t test Methods 0.000 description 1
230000002123 temporal effect Effects 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000036575 thermal burns Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
229930003799 tocopherol Natural products 0.000 description 1
235000010384 tocopherol Nutrition 0.000 description 1
229960001295 tocopherol Drugs 0.000 description 1
239000011732 tocopherol Substances 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
229960001722 verapamil Drugs 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
239000011709 vitamin E Chemical class 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- 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
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Ophthalmology & Optometry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)

ZA200103236A 1998-10-27 2001-04-20 Treatment of disorders of the outer retina. ZA200103236B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US10571298P	1998-10-27	1998-10-27

Publications (1)

Publication Number	Publication Date
ZA200103236B true ZA200103236B (en)	2001-10-23

Family

ID=22307389

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200103236A ZA200103236B (en)	1998-10-27	2001-04-20	Treatment of disorders of the outer retina.

Country Status (12)

Country	Link
US (1)	US6509355B1 (fr)
EP (1)	EP1126850A4 (fr)
JP (1)	JP2002528416A (fr)
KR (1)	KR20020002356A (fr)
CN (1)	CN1324240A (fr)
AR (1)	AR023687A1 (fr)
AU (1)	AU761824B2 (fr)
BR (1)	BR9914848A (fr)
CA (1)	CA2347863C (fr)
TR (1)	TR200101149T2 (fr)
WO (1)	WO2000024396A1 (fr)
ZA (1)	ZA200103236B (fr)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20050009884A1 (en) *	1997-06-30	2005-01-13	Dreyer Evan B.	Calcium blockers to treat proliferative retinal diseases
AU727080B2 (en) *	1997-06-30	2000-11-30	Allergan, Inc.	Calcium blockers to treat proliferative vitreoretinopathy
JP2002182418A (ja) *	2000-12-11	2002-06-26	Konica Corp	画像形成方法、画像形成装置
WO2002070478A1 (fr)	2001-03-06	2002-09-12	Astrazeneca Ab	Dérivés indolone capable de dégrader des vaisseaux
FR2822706A1 (fr) *	2001-03-29	2002-10-04	Univ Pasteur	Utilisation de composes organiques antagonistes de recepteurs pour le traitement de la degenerescence retinienne
US7273889B2 (en) *	2002-09-25	2007-09-25	Innovative Drug Delivery Systems, Inc.	NMDA receptor antagonist formulation with reduced neurotoxicity
US20050031652A1 (en) *	2003-02-25	2005-02-10	Allergan, Inc.	Compositions and methods comprising memantine and polyanionic polymers
US20050283109A1 (en) *	2003-03-07	2005-12-22	Peyman Gholam A	Method and apparatus for lacrimal canal obstruction
US7220224B1 (en) *	2003-03-07	2007-05-22	Minu, Llc	Retinal translocation and fixation using adhesive material
US20050130878A1 (en) *	2003-11-26	2005-06-16	Alcon, Inc.	Prevention of photic injury by administering a TACE inhibitor
US20050277698A1 (en) *	2004-01-05	2005-12-15	Hughes Patrick M	Memantine delivery to the back of the eye
US9693967B2 (en) *	2005-09-07	2017-07-04	Southwest Research Institute	Biodegradable microparticle pharmaceutical formulations exhibiting improved released rates
US7758778B2 (en) *	2005-09-07	2010-07-20	Southwest Research Institute	Methods for preparing biodegradable microparticle formulations containing pharmaceutically active agents
US7261529B2 (en) *	2005-09-07	2007-08-28	Southwest Research Institute	Apparatus for preparing biodegradable microparticle formulations containing pharmaceutically active agents
WO2008098027A2 (fr) *	2007-02-06	2008-08-14	Allergan, Inc.	Traitement d'affections rétiniennes ischémiques avec de la mémantine
JP2023511370A (ja)	2020-01-22	2023-03-17	シーロスセラピューティクス，インコーポレイテッド	Ｎｍｄａ拮抗薬の副作用の低減

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2534580A1 (fr)	1982-10-13	1984-04-20	Synthelabo	Derives de phenyl-1 piperidino-2 propanol, leur preparation, et medicaments qui les contiennent
FR2717080B1 (fr) *	1994-03-09	1996-12-13	Synthelabo	Utilisation de l'éliprodil et de ses énantiomères pour la préparation de médicaments utiles dans le traitement des neuropathies périphériques et des maladies neurodégénératives centrales.
US5710165A (en) *	1994-07-06	1998-01-20	Synthelabo	Use of polyamine antagonists for the treatment of glaucoma
US5604244A (en) *	1995-06-07	1997-02-18	Alcon Laboratories, Inc.	Intraocular irrigating solution containing a polyamine antagonist
SI0848707T1 (en)	1995-09-08	2000-02-29	Sanofi-Synthelabo	4-(cycloalkyl)piperidines and 4-(cycloalkylalkyl)-piperidines derivatives, preparation thereof and therapeutical applications thereof
FR2738567B1 (fr)	1995-09-08	1997-10-17	Synthelabo	Derives de alpha-phenylpiperidine-1-propanol, leur preparation et leur application en therapeutique
JP2000507205A (ja) *	1996-01-02	2000-06-13	シンテラボ	眼の虚血障害の治療薬の製造のためのポリアミン部位拮抗物質の使用
AU727080B2 (en) *	1997-06-30	2000-11-30	Allergan, Inc.	Calcium blockers to treat proliferative vitreoretinopathy

1999
- 1999-10-20 JP JP2000578006A patent/JP2002528416A/ja active Pending
- 1999-10-20 US US09/807,805 patent/US6509355B1/en not_active Expired - Lifetime
- 1999-10-20 AU AU15169/00A patent/AU761824B2/en not_active Ceased
- 1999-10-20 BR BR9914848-0A patent/BR9914848A/pt not_active Application Discontinuation
- 1999-10-20 WO PCT/US1999/024502 patent/WO2000024396A1/fr not_active Ceased
- 1999-10-20 CN CN99812628A patent/CN1324240A/zh active Pending
- 1999-10-20 CA CA002347863A patent/CA2347863C/fr not_active Expired - Fee Related
- 1999-10-20 TR TR2001/01149T patent/TR200101149T2/xx unknown
- 1999-10-20 EP EP99957471A patent/EP1126850A4/fr not_active Ceased
- 1999-10-20 KR KR1020017005201A patent/KR20020002356A/ko not_active Withdrawn
- 1999-10-26 AR ARP990105400A patent/AR023687A1/es not_active Application Discontinuation
2001
- 2001-04-20 ZA ZA200103236A patent/ZA200103236B/en unknown

Also Published As

Publication number	Publication date
AR023687A1 (es)	2002-09-04
US6509355B1 (en)	2003-01-21
EP1126850A4 (fr)	2003-01-15
AU1516900A (en)	2000-05-15
CN1324240A (zh)	2001-11-28
CA2347863A1 (fr)	2000-05-04
TR200101149T2 (tr)	2001-10-22
CA2347863C (fr)	2009-05-05
EP1126850A1 (fr)	2001-08-29
JP2002528416A (ja)	2002-09-03
WO2000024396A1 (fr)	2000-05-04
AU761824B2 (en)	2003-06-12
WO2000024396A9 (fr)	2000-09-28
BR9914848A (pt)	2001-07-10
KR20020002356A (ko)	2002-01-09

Publication	Publication Date	Title
AU761824B2 (en)	2003-06-12	Treatment of disorders of the outer retina
EP1263504B1 (fr)	2003-08-20	Utilisation de composes a activite agoniste sur le recepteur 5-ht1a destines au traitement des affections de la retine externe
US8710102B2 (en)	2014-04-29	Use of beta-adrenoceptor antagonists for the manufacture of a medicament of the treatment of disorders of the outer retina
US20100168121A1 (en)	2010-07-01	Compounds with 5-ht1a activity useful for treating disorders of the outer retina
AU2001245310A1 (en)	2001-12-13	Compounds with 5-HT1A activity useful for treating disorders of the outer retina
MXPA01004175A (en)	2002-03-05	Treatment of disorders of the outer retina
US20110160308A1 (en)	2011-06-30	Use of Monoamine Oxidase Inhibitors to Treat Outer Retina Disorders
HK1051504B (en)	2004-04-23	Use of compounds with 5-ht1a activity useful for treating disorders of the outer retina