ES2333339T3 - Tratamiento de trastornos de la retina causados por la disminucion del flujo sanguineo con derivados de quinoxalina. - Google Patents
Tratamiento de trastornos de la retina causados por la disminucion del flujo sanguineo con derivados de quinoxalina. Download PDFInfo
- Publication number
- ES2333339T3 ES2333339T3 ES05028359T ES05028359T ES2333339T3 ES 2333339 T3 ES2333339 T3 ES 2333339T3 ES 05028359 T ES05028359 T ES 05028359T ES 05028359 T ES05028359 T ES 05028359T ES 2333339 T3 ES2333339 T3 ES 2333339T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- nerve
- injury
- carbon atoms
- use according
- Prior art date
- 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 - Lifetime
Links
- 210000001525 retina Anatomy 0.000 title claims abstract description 15
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical class N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 title claims description 5
- 230000017531 blood circulation Effects 0.000 title claims description 4
- 238000011282 treatment Methods 0.000 title description 16
- 210000001328 optic nerve Anatomy 0.000 claims abstract description 25
- 229940079593 drug Drugs 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 20
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- -1 2-imidazolin-2-ylamino group Chemical group 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 26
- 230000003902 lesion Effects 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 9
- 230000004224 protection Effects 0.000 claims description 7
- 239000000556 agonist Substances 0.000 claims description 6
- 150000003252 quinoxalines Chemical class 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 claims description 3
- 230000008499 blood brain barrier function Effects 0.000 claims description 3
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 3
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- 230000001384 anti-glaucoma Effects 0.000 claims description 2
- 239000002876 beta blocker Substances 0.000 claims description 2
- 229940097320 beta blocking agent Drugs 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 239000006193 liquid solution Substances 0.000 claims 1
- 239000000472 muscarinic agonist Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 abstract description 15
- 230000004112 neuroprotection Effects 0.000 abstract description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 abstract description 3
- 230000030833 cell death Effects 0.000 abstract description 2
- 210000005036 nerve Anatomy 0.000 description 32
- 208000014674 injury Diseases 0.000 description 31
- 208000027418 Wounds and injury Diseases 0.000 description 30
- 230000006378 damage Effects 0.000 description 26
- 238000005259 measurement Methods 0.000 description 20
- 208000010412 Glaucoma Diseases 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 17
- 210000001508 eye Anatomy 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 15
- 229930195712 glutamate Natural products 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 241000700159 Rattus Species 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000006835 compression Effects 0.000 description 11
- 238000007906 compression Methods 0.000 description 11
- 210000003050 axon Anatomy 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000002503 metabolic effect Effects 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 230000004410 intraocular pressure Effects 0.000 description 8
- 230000001537 neural effect Effects 0.000 description 7
- 239000004090 neuroprotective agent Substances 0.000 description 7
- 230000002207 retinal effect Effects 0.000 description 7
- 208000028389 Nerve injury Diseases 0.000 description 6
- 230000036982 action potential Effects 0.000 description 6
- 230000007547 defect Effects 0.000 description 6
- 230000000763 evoking effect Effects 0.000 description 6
- 230000008764 nerve damage Effects 0.000 description 6
- 235000020945 retinal Nutrition 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 230000000007 visual effect Effects 0.000 description 6
- 206010029174 Nerve compression Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 210000002159 anterior chamber Anatomy 0.000 description 4
- 210000001742 aqueous humor Anatomy 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 230000003412 degenerative effect Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 210000004498 neuroglial cell Anatomy 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 210000003625 skull Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229920008347 Cellulose acetate propionate Polymers 0.000 description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 3
- 206010061323 Optic neuropathy Diseases 0.000 description 3
- 208000004732 Systemic Vasculitis Diseases 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- 229960002896 clonidine Drugs 0.000 description 3
- 238000009470 controlled atmosphere packaging Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 208000020911 optic nerve disease Diseases 0.000 description 3
- 239000003223 protective agent Substances 0.000 description 3
- 238000013222 sprague-dawley male rat Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000000857 visual cortex Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010030043 Ocular hypertension Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 230000002518 glial effect Effects 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229950006238 nadide Drugs 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 230000001067 neuroprotector Effects 0.000 description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000003334 potential effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000000926 separation method Methods 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
- 210000003437 trachea Anatomy 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 101500000960 Bacillus anthracis Protective antigen PA-63 Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000031969 Eye Hemorrhage Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010058490 Hyperoxia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010065630 Iris neovascularisation Diseases 0.000 description 1
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 1
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 1
- 208000030768 Optic nerve injury Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003522 acrylic cement Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000001609 comparable effect Effects 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000009509 cortical damage Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 1
- 229950004794 dizocilpine Drugs 0.000 description 1
- 230000004406 elevated intraocular pressure Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000013305 flexible fiber Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000013534 fluorescein angiography Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000000222 hyperoxic effect Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 230000019948 ion homeostasis Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229940039412 ketalar Drugs 0.000 description 1
- VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- WSMDMNKPSPSRKB-UHFFFAOYSA-N n-(4,5-dihydro-1h-imidazol-2-yl)-6-methylquinoxalin-2-amine Chemical compound C1=NC2=CC(C)=CC=C2N=C1NC1=NCCN1 WSMDMNKPSPSRKB-UHFFFAOYSA-N 0.000 description 1
- 210000000537 nasal bone Anatomy 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 210000003733 optic disk Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 210000000977 primary visual cortex Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 230000010344 pupil dilation Effects 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000033287 response to anoxia Effects 0.000 description 1
- 230000024288 response to hyperoxia Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 150000003726 retinal derivatives Chemical class 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 210000001957 retinal vein Anatomy 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000004393 visual impairment Effects 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/496,262 US5856329A (en) | 1995-06-28 | 1995-06-28 | Method of using (2-imidazolin-2-ylamino) quinoxalines in treating ocular neural injury |
| US496262 | 1995-06-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2333339T3 true ES2333339T3 (es) | 2010-02-19 |
Family
ID=23971914
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES05028359T Expired - Lifetime ES2333339T3 (es) | 1995-06-28 | 1996-06-17 | Tratamiento de trastornos de la retina causados por la disminucion del flujo sanguineo con derivados de quinoxalina. |
| ES96923317T Expired - Lifetime ES2262157T5 (es) | 1995-06-28 | 1996-06-17 | Método de uso (2-imidazolina-2-ylamino) de quinoxalinas para tratar lesión ocular neural. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES96923317T Expired - Lifetime ES2262157T5 (es) | 1995-06-28 | 1996-06-17 | Método de uso (2-imidazolina-2-ylamino) de quinoxalinas para tratar lesión ocular neural. |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US5856329A (enExample) |
| EP (3) | EP1611891B1 (enExample) |
| JP (3) | JP4621306B2 (enExample) |
| KR (1) | KR19990028403A (enExample) |
| CN (3) | CN1197391A (enExample) |
| AT (2) | ATE322267T1 (enExample) |
| AU (1) | AU715742B2 (enExample) |
| BR (1) | BR9609219A (enExample) |
| CA (1) | CA2225626C (enExample) |
| DE (2) | DE69636012T3 (enExample) |
| DK (1) | DK0835110T4 (enExample) |
| ES (2) | ES2333339T3 (enExample) |
| PT (1) | PT835110E (enExample) |
| WO (1) | WO1997001339A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294563B1 (en) | 1994-10-27 | 2001-09-25 | Allergan Sales, Inc. | Combinations of prostaglandins and brimonidine or derivatives thereof |
| US6194415B1 (en) * | 1995-06-28 | 2001-02-27 | Allergan Sales, Inc. | Method of using (2-imidazolin-2-ylamino) quinoxoalines in treating neural injury |
| US5856329A (en) * | 1995-06-28 | 1999-01-05 | Allergan | Method of using (2-imidazolin-2-ylamino) quinoxalines in treating ocular neural injury |
| WO1999025350A1 (en) * | 1997-11-14 | 1999-05-27 | Alcon Laboratories, Inc. | Treatment of diabetic retinopathy |
| WO2004073708A1 (en) | 1998-12-17 | 2004-09-02 | Dean Thomas R | Brinzolamide and brimonidine for treating ocular conditions |
| US6247473B1 (en) | 1999-02-18 | 2001-06-19 | Third Millenium Trust | System and method for testing the neuroprotective or neuroregenerative effects of drugs |
| JP2003514015A (ja) * | 1999-11-12 | 2003-04-15 | アルコン，インコーポレイテッド | 眼の状態を処置するためのニューロフィリンリガンド |
| US6294553B1 (en) * | 2000-02-15 | 2001-09-25 | Allergan Sales, Inc. | Method for treating ocular pain |
| DE10013318A1 (de) * | 2000-03-17 | 2001-09-20 | Merck Patent Gmbh | Formulierung enthaltend Chinoxalinderivate |
| WO2002005853A2 (en) * | 2000-07-14 | 2002-01-24 | Allergan, Inc. | Compositions containing alpha-2-adrenergic agonist components |
| DE10035620B4 (de) * | 2000-07-21 | 2005-07-14 | *Acri.Tec Gesellschaft für ophthalmologische Produkte mbH | Verwendung von Taurin als neuroprotektives Agens in der Ophthalmologie |
| AU2002248284A1 (en) * | 2000-11-01 | 2002-08-06 | Allergan, Inc. | Compositions for treatment of ocular neovascularization |
| US20030082183A1 (en) * | 2000-11-01 | 2003-05-01 | Wheeler Larry A. | Methods and compositions for treatment of ocular neovascularization and neural injury |
| US7642258B2 (en) * | 2002-04-19 | 2010-01-05 | Allergan, Inc. | Combination of brimonidine and timolol for topical ophthalmic use |
| US7030149B2 (en) * | 2002-04-19 | 2006-04-18 | Allergan, Inc. | Combination of brimonidine timolol for topical ophthalmic use |
| US8529927B2 (en) * | 2004-04-30 | 2013-09-10 | Allergan, Inc. | Alpha-2 agonist polymeric drug delivery systems |
| US20050244463A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular vasculopathies |
| US8425929B2 (en) * | 2004-04-30 | 2013-04-23 | Allergan, Inc. | Sustained release intraocular implants and methods for preventing retinal dysfunction |
| AU2005257883A1 (en) * | 2004-06-04 | 2006-01-05 | Washington University | Methods and compositions for treating neuropathies |
| US7534795B2 (en) * | 2005-10-25 | 2009-05-19 | Allergan, Inc. | Compounds and their use related to compositions for treating disease |
| US8067433B2 (en) | 2005-11-09 | 2011-11-29 | Zalicus Inc. | Methods, compositions, and kits for the treatment of ophthalmic disorders |
| CA2641501A1 (en) * | 2006-02-06 | 2007-08-16 | Nicox S.A. | Nitrooxy-comprising derivatives of apraclonidine and brimodnidine as al pha2 -adrenergic receptor agonists |
| US8969415B2 (en) * | 2006-12-01 | 2015-03-03 | Allergan, Inc. | Intraocular drug delivery systems |
| WO2009023752A1 (en) * | 2007-08-15 | 2009-02-19 | Allergan, Inc. | Adrenergic compounds |
| US9095506B2 (en) | 2008-11-17 | 2015-08-04 | Allergan, Inc. | Biodegradable alpha-2 agonist polymeric implants and therapeutic uses thereof |
| NZ628266A (en) | 2009-11-09 | 2016-02-26 | Allergan Inc | Compositions and methods for stimulating hair growth |
| US9522153B2 (en) | 2009-12-22 | 2016-12-20 | Allergan, Inc. | Compositions and methods for lowering intraocular pressure |
| JP6511401B2 (ja) | 2013-02-15 | 2019-05-15 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | 持続型薬物送達インプラント |
| WO2015129809A1 (ja) * | 2014-02-28 | 2015-09-03 | 国立大学法人京都大学 | 虚血性眼疾患の処置用の医薬組成物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4029792A (en) * | 1972-02-29 | 1977-06-14 | Pfizer Inc. | (2-Imidazolin-2-ylamino) substituted -quinoxalines and -quinazolines as antihypertensive agents |
| US4587257A (en) * | 1984-12-14 | 1986-05-06 | Alcon Laboratories, Inc. | Control of ocular bleeding using clonidine derivatives |
| US5180721A (en) * | 1989-05-22 | 1993-01-19 | Allergan, Inc. | Combinations of selective alpha-adrenergic agonists and antagonists useful in lowering intraocular pressure |
| US5021410A (en) * | 1989-05-22 | 1991-06-04 | Allergan, Inc. | Combinations of selective alpha-adrenergic agonists and antagonists useful in lowering intraocular pressure |
| US5077292A (en) * | 1989-10-12 | 1991-12-31 | Allergan, Inc. | (2-imidazolin-2-ylamino) tetrahydroquinoxalines and methods for using same |
| US5021416A (en) * | 1989-10-31 | 1991-06-04 | Allergan, Inc. | Method for using (2-imidazolin-2-ylamino) quinoxalines to reduce or maintain intraocular pressure |
| US5215991A (en) * | 1990-01-26 | 1993-06-01 | Allergan, Inc. | Combination of selective alpha-adrenergic agonists and Na+ /H+ ex |
| CN1137755A (zh) † | 1993-12-17 | 1996-12-11 | 普罗克特和甘保尔公司 | 用作α-2肾上腺素能受体兴奋剂的6-(2-咪唑啉基氨基)喹喔啉化合物 |
| WO1996013267A2 (en) * | 1994-10-27 | 1996-05-09 | Allergan | Combinations of prostaglandins and brimonidine or derivatives thereof for the treatment of glaucoma |
| US5856329A (en) * | 1995-06-28 | 1999-01-05 | Allergan | Method of using (2-imidazolin-2-ylamino) quinoxalines in treating ocular neural injury |
| US6194415B1 (en) * | 1995-06-28 | 2001-02-27 | Allergan Sales, Inc. | Method of using (2-imidazolin-2-ylamino) quinoxoalines in treating neural injury |
-
1995
- 1995-06-28 US US08/496,262 patent/US5856329A/en not_active Expired - Lifetime
-
1996
- 1996-06-17 KR KR1019970709719A patent/KR19990028403A/ko not_active Ceased
- 1996-06-17 CA CA002225626A patent/CA2225626C/en not_active Expired - Lifetime
- 1996-06-17 AT AT96923317T patent/ATE322267T1/de active
- 1996-06-17 DE DE69636012T patent/DE69636012T3/de not_active Expired - Lifetime
- 1996-06-17 CN CN96196328A patent/CN1197391A/zh active Pending
- 1996-06-17 AU AU63864/96A patent/AU715742B2/en not_active Expired
- 1996-06-17 CN CN200910178530A patent/CN101683343A/zh active Pending
- 1996-06-17 CN CN2006101011051A patent/CN1943577B/zh not_active Expired - Lifetime
- 1996-06-17 DK DK96923317.0T patent/DK0835110T4/da active
- 1996-06-17 AT AT05028359T patent/ATE447956T1/de not_active IP Right Cessation
- 1996-06-17 ES ES05028359T patent/ES2333339T3/es not_active Expired - Lifetime
- 1996-06-17 JP JP50445497A patent/JP4621306B2/ja not_active Expired - Lifetime
- 1996-06-17 WO PCT/US1996/010468 patent/WO1997001339A1/en not_active Ceased
- 1996-06-17 EP EP05076936A patent/EP1611891B1/en not_active Expired - Lifetime
- 1996-06-17 BR BR9609219A patent/BR9609219A/pt not_active Application Discontinuation
- 1996-06-17 DE DE69638072T patent/DE69638072D1/de not_active Expired - Lifetime
- 1996-06-17 PT PT96923317T patent/PT835110E/pt unknown
- 1996-06-17 EP EP05028359A patent/EP1642581B1/en not_active Expired - Lifetime
- 1996-06-17 ES ES96923317T patent/ES2262157T5/es not_active Expired - Lifetime
- 1996-06-17 EP EP96923317A patent/EP0835110B2/en not_active Expired - Lifetime
-
2006
- 2006-01-05 JP JP2006000809A patent/JP2006241138A/ja not_active Withdrawn
-
2010
- 2010-10-15 JP JP2010232760A patent/JP2011042668A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2333339T3 (es) | Tratamiento de trastornos de la retina causados por la disminucion del flujo sanguineo con derivados de quinoxalina. | |
| ES2251968T3 (es) | (2-imidazolin-2-ilamino)quinoxalinas para el tratamiento de lesiones neuronales. | |
| ES2211197T3 (es) | Uso de derivados de estaurosporina para tratar enfermedades neovasculares oculares. | |
| ES2317650T3 (es) | Farmacos para mejorar trastornos circulatorios oculares. | |
| ES2224597T3 (es) | Agentes que mejoran la circulacion optica papilar. | |
| MXPA97010480A (en) | Method of use of (2-imidazolin-2-ilamino) quinoxalines to treat opt nerve injury | |
| Leffler et al. | 14. Angle-Closure Glaucoma Since 1871 | |
| Pouliquen et al. | ii AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE, 1970 | |
| VEASEY | LINICAL AND HISTOLOGIC OBSERVATIONS ON SYMPATHETIC OPHTHALMIA. | |
| HK1142830A (en) | Use of (2-imidazolin-2ylamino) quinoxalines for the manufacture of a medicament | |
| JACOBS | CHAPTER VIII THE CORNEA AND SCLERA MAX W. JACOBS, MD ST. LOUIS | |
| HK1016073A (en) | Method of using (2-imidazolin-2-ylamino) quinoxalines in treating ocular neural injury |