ZA200102157B - Serotonergic 5HT2 agonists for treating glaucoma. - Google Patents
Serotonergic 5HT2 agonists for treating glaucoma. Download PDFInfo
- Publication number
- ZA200102157B ZA200102157B ZA200102157A ZA200102157A ZA200102157B ZA 200102157 B ZA200102157 B ZA 200102157B ZA 200102157 A ZA200102157 A ZA 200102157A ZA 200102157 A ZA200102157 A ZA 200102157A ZA 200102157 B ZA200102157 B ZA 200102157B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- sht
- composition
- compounds
- weight percent
- Prior art date
Links
- 208000010412 Glaucoma Diseases 0.000 title claims description 13
- 230000000862 serotonergic effect Effects 0.000 title description 9
- 239000003478 serotonin 5-HT2 receptor agonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 26
- 239000000556 agonist Substances 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 18
- 239000000018 receptor agonist Substances 0.000 claims description 8
- 229940044601 receptor agonist Drugs 0.000 claims description 8
- OGNJZVNNKBZFRM-UHFFFAOYSA-N 1-(5-methoxy-1H-indol-3-yl)-2-propanamine Chemical compound COC1=CC=C2NC=C(CC(C)N)C2=C1 OGNJZVNNKBZFRM-UHFFFAOYSA-N 0.000 claims description 5
- -1 a-Methylserotonin Chemical compound 0.000 claims description 5
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 claims description 5
- 230000003547 miosis Effects 0.000 claims description 5
- 150000003180 prostaglandins Chemical class 0.000 claims description 5
- BGMZUEKZENQUJY-SSDOTTSWSA-N (2r)-1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine Chemical group COC1=CC(C[C@@H](C)N)=C(OC)C=C1I BGMZUEKZENQUJY-SSDOTTSWSA-N 0.000 claims description 3
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 claims description 3
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 claims description 3
- 229960002610 apraclonidine Drugs 0.000 claims description 3
- IEJXVRYNEISIKR-UHFFFAOYSA-N apraclonidine Chemical compound ClC1=CC(N)=CC(Cl)=C1NC1=NCCN1 IEJXVRYNEISIKR-UHFFFAOYSA-N 0.000 claims description 3
- 229960003679 brimonidine Drugs 0.000 claims description 3
- 239000003604 miotic agent Substances 0.000 claims description 3
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 230000004410 intraocular pressure Effects 0.000 description 29
- 102000005962 receptors Human genes 0.000 description 27
- 108020003175 receptors Proteins 0.000 description 27
- 239000005557 antagonist Substances 0.000 description 13
- 241000283973 Oryctolagus cuniculus Species 0.000 description 11
- 238000009472 formulation Methods 0.000 description 9
- 241000282414 Homo sapiens Species 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 230000027455 binding Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229960000367 inositol Drugs 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 229940076279 serotonin Drugs 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 102000014384 Type C Phospholipases Human genes 0.000 description 4
- 108010079194 Type C Phospholipases Proteins 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229940054534 ophthalmic solution Drugs 0.000 description 4
- 150000003906 phosphoinositides Chemical class 0.000 description 4
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- WKZLNEWVIAGNAW-UHFFFAOYSA-N 5-Carboxyamidotryptamine Chemical compound C1=C(C(N)=O)C=C2C(CCN)=CNC2=C1 WKZLNEWVIAGNAW-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102000030621 adenylate cyclase Human genes 0.000 description 3
- 108060000200 adenylate cyclase Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- HIHZDNKKIUQQSC-UHFFFAOYSA-N 6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propylamino]-1,3,5-trimethylpyrimidine-2,4-dione Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2C)C)CC1 HIHZDNKKIUQQSC-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 239000006091 Macor Substances 0.000 description 2
- RLJFTICUTYVZDG-UHFFFAOYSA-N Methiothepine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2CC1N1CCN(C)CC1 RLJFTICUTYVZDG-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 230000003491 cAMP production Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229960002464 fluoxetine Drugs 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 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
- 230000003834 intracellular effect Effects 0.000 description 2
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 2
- 229960005417 ketanserin Drugs 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 238000001525 receptor binding assay Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229960002668 sodium chloride Drugs 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 1
- MMWCIQZXVOZEGG-UHFFFAOYSA-N 1,4,5-IP3 Natural products OC1C(O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(O)C1OP(O)(O)=O MMWCIQZXVOZEGG-UHFFFAOYSA-N 0.000 description 1
- GGNCUSDIUUCNKE-RSAXXLAASA-N 3-(1,3-benzodioxol-5-yloxy)-n-[[(3s)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine;hydrochloride Chemical compound Cl.C1=C2OCOC2=CC(OCCCNC[C@@H]2OC3=CC=CC=C3OC2)=C1 GGNCUSDIUUCNKE-RSAXXLAASA-N 0.000 description 1
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- MMWCIQZXVOZEGG-XJTPDSDZSA-N D-myo-Inositol 1,4,5-trisphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=O MMWCIQZXVOZEGG-XJTPDSDZSA-N 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 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
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
- 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 1
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 1
- 206010030043 Ocular hypertension Diseases 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KCLANYCVBBTKTO-UHFFFAOYSA-N Proparacaine Chemical compound CCCOC1=CC=C(C(=O)OCCN(CC)CC)C=C1N KCLANYCVBBTKTO-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000004420 blood-aqueous barrier Effects 0.000 description 1
- 210000002164 blood-aqueous barrier Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 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
- 238000010828 elution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone 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
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 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
- 229960001186 methysergide Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229960003981 proparacaine Drugs 0.000 description 1
- 229940035613 prozac Drugs 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 1
- 229960003708 sumatriptan Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 230000002792 vascular Effects 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
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10106798P | 1998-09-18 | 1998-09-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200102157B true ZA200102157B (en) | 2003-03-05 |
Family
ID=22282920
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200102157A ZA200102157B (en) | 1998-09-18 | 2001-03-15 | Serotonergic 5HT2 agonists for treating glaucoma. |
Country Status (18)
Country | Link |
---|---|
US (2) | US6664286B1 (de) |
EP (1) | EP1112106B1 (de) |
JP (1) | JP2002526443A (de) |
KR (1) | KR20010073153A (de) |
CN (1) | CN1269484C (de) |
AR (1) | AR020442A1 (de) |
AT (1) | ATE310566T1 (de) |
AU (1) | AU755119B2 (de) |
BR (1) | BR9913800A (de) |
CA (1) | CA2344150A1 (de) |
DE (1) | DE69928542T2 (de) |
DK (1) | DK1112106T3 (de) |
ES (1) | ES2252978T3 (de) |
HK (1) | HK1038516A1 (de) |
TR (1) | TR200100754T2 (de) |
TW (1) | TWI229602B (de) |
WO (1) | WO2000016761A2 (de) |
ZA (1) | ZA200102157B (de) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6960579B1 (en) | 1998-05-19 | 2005-11-01 | Alcon Manufacturing, Ltd. | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders |
US6806285B1 (en) | 2000-03-17 | 2004-10-19 | Alcon, Inc. | 5-Hydroxyl indole derivatives for treating glaucoma |
BR0017163A (pt) * | 2000-03-17 | 2003-01-14 | Alcon Inc | Derivados 5-hidróxi-indazol para tratamento do glaucoma |
CN1450994A (zh) * | 2000-03-17 | 2003-10-22 | 爱尔康公司 | 用于治疗青光眼的6-羟基-吲唑衍生物 |
AU2001219185A1 (en) | 2000-03-17 | 2001-10-03 | Alcon, Inc. | 2-acylaminobenzimidazole derivatives for treating glaucoma |
AU2001216035A1 (en) * | 2000-03-17 | 2001-10-03 | Alcon Universal Ltd. | 5-hydroxy indole derivatives for treating glaucoma |
US7012090B1 (en) | 2000-03-17 | 2006-03-14 | Alcon, Inc. | Pyranoindoles for treating glaucoma |
US7005443B1 (en) * | 2000-03-17 | 2006-02-28 | Alcon, Inc. | 5-Hydroxy indazole derivatives for treating glaucoma |
US6956036B1 (en) | 2000-03-17 | 2005-10-18 | Alcon, Inc. | 6-hydroxy-indazole derivatives for treating glaucoma |
US6927233B1 (en) * | 2000-03-17 | 2005-08-09 | Alcon, Inc. | 5ht2 agonists for controlling IOP and treating glaucoma |
US6903081B2 (en) * | 2000-03-31 | 2005-06-07 | Purdue Research Foundation | Phosphoramidates and methods therefor |
WO2002098860A1 (en) | 2001-06-01 | 2002-12-12 | Alcon, Inc. | Novel fused indazoles and indoles and their use for the treatment of glaucoma |
CA2447479A1 (en) | 2001-06-01 | 2002-12-12 | Alcon, Inc. | Novel arylaminopropane analogues and their use for the treatment of glaucoma |
DE60209486T2 (de) | 2001-06-01 | 2006-08-03 | Alcon Inc. | Pyranoindazole und ihre verwendung in der glaukombehandlung |
US6884816B2 (en) * | 2001-08-31 | 2005-04-26 | Alcon, Inc. | Hydroxy substituted fused naphthyl-azoles and fused indeno-azoles and their use for the treatment of glaucoma |
TW593302B (en) | 2001-12-20 | 2004-06-21 | Alcon Inc | Novel benzodifuranimidazoline and benzofuranimidazoline derivatives and their use for the treatment of glaucoma |
AU2003262931B2 (en) * | 2002-08-30 | 2008-06-26 | Alcon, Inc. | Substituted 5-chroman-5-yl-ethylamine compounds and their use for the treatment of glaucoma |
CA2492468A1 (en) * | 2002-09-24 | 2004-04-08 | Virginia Commonwealth University | .beta.-hydroxyphenylalkylamines and their use for treating glaucoma |
CA2506204A1 (en) | 2002-12-13 | 2004-07-01 | Alcon, Inc. | Novel benzopyran analogs and their use for the treatment of glaucoma |
WO2005053688A1 (en) * | 2003-11-26 | 2005-06-16 | Alcon, Inc. | Substituted furo[2,3-g] indazoles for the treatment of glaucoma |
US7338972B1 (en) | 2003-12-15 | 2008-03-04 | Alcon, Inc. | Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma |
WO2005058911A2 (en) * | 2003-12-15 | 2005-06-30 | Alcon, Inc. | Substituted [1,4]oxazino[2,3-g]indazoles for the treatment of glaucoma |
US7129257B1 (en) | 2003-12-15 | 2006-10-31 | Alcon, Inc. | Pyrazolo[3,4- e]benzoxazoles for the treatment of glaucoma |
EP1744784A2 (de) * | 2004-05-11 | 2007-01-24 | Becton, Dickinson and Company | Schmerzmittelformulierungen und verfahren zu deren anwendung |
EP2400300A1 (de) | 2004-08-25 | 2011-12-28 | Takeda Pharmaceutical Company Limited | Screeningverfahren von Mitteln zur Prävention/Behandlung von stressbedingter Harninkontinenz |
WO2006062839A1 (en) * | 2004-12-08 | 2006-06-15 | Alcon, Inc. | Use of dioxindoindazoles and dioxoloindazoles for treating glaucoma |
US20060211700A1 (en) * | 2005-03-21 | 2006-09-21 | Alcon, Inc. | (R)-8,9-dichloro-2,3,4,4a-tetrahydro-1H,6H-pyrazino[1,2-a]quinoxalin-5-one for controlling IOP and treating glaucoma |
TW200744567A (en) * | 2005-09-23 | 2007-12-16 | Alcon Inc | Phenylethylamine analogs and their use for treating glaucoma |
WO2007132841A1 (ja) | 2006-05-16 | 2007-11-22 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物およびその用途 |
WO2007149728A2 (en) * | 2006-06-20 | 2007-12-27 | Alcon Research, Ltd. | Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma |
MY167602A (en) | 2007-11-01 | 2018-09-20 | Acucela Inc | Amine derivatives compounds for treating ophthalmic diseases and disorders |
WO2009063992A1 (ja) | 2007-11-15 | 2009-05-22 | Takeda Pharmaceutical Company Limited | 縮合ピリジン誘導体およびその用途 |
US9642819B2 (en) * | 2008-07-10 | 2017-05-09 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical | Low dosage serotonin 5-HT2A receptor agonist to suppress inflammation |
US8299079B2 (en) | 2009-05-22 | 2012-10-30 | Kaufman Herbert E | Preparations and methods for ameliorating or reducing presbyopia |
JPWO2011071136A1 (ja) | 2009-12-11 | 2013-04-22 | アステラス製薬株式会社 | 線維筋痛症治療剤 |
TW201210584A (en) | 2010-08-18 | 2012-03-16 | Alcon Res Ltd | Bradykinin receptor agonists and uses thereof to treat ocular hypertension and glaucoma |
GB2571696B (en) | 2017-10-09 | 2020-05-27 | Compass Pathways Ltd | Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced |
JPWO2019131902A1 (ja) | 2017-12-27 | 2020-12-10 | 武田薬品工業株式会社 | 腹圧性尿失禁および便失禁の治療薬 |
WO2020212952A1 (en) | 2019-04-17 | 2020-10-22 | Compass Pathfinder Limited | Treatment of depression and other various disorders with psilocybin |
WO2024010765A1 (en) * | 2022-07-05 | 2024-01-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Compositions for treating 5-ht2 conditions and methods of using the same |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4487773A (en) | 1981-03-16 | 1984-12-11 | Mead Johnson & Company | 1,2,4-Triazol-3-one antidepressants |
US4742054A (en) * | 1982-11-23 | 1988-05-03 | Naftchi Nosrat E | Treatment of mammals suffering from damage to the central nervous system |
US4659706A (en) | 1985-12-20 | 1987-04-21 | Smithkline Beckman Corporation | Sulfinyl and sulfonyl substituted 3-benzazepines |
US5011846A (en) | 1988-02-23 | 1991-04-30 | Merrell Dow Pharmaceuticals Inc. | Medicament compositions derived from quinolizine and quinolizinone and methods of use thereof |
DE69018332T2 (de) | 1989-07-28 | 1995-10-26 | Nippon Oil Co Ltd | Verfahren zur kontinuierlichen Herstellung eines Polyethylenmaterials mit hoher Festigkeit und hohem Modul. |
US5578612A (en) | 1990-10-15 | 1996-11-26 | Pfizer Inc. | Indole derivatives |
US5545644A (en) | 1990-10-15 | 1996-08-13 | Pfizer Inc. | Indole derivatives |
WO1992020338A1 (en) | 1991-05-10 | 1992-11-26 | Merrell Dow Pharmaceuticals Inc. | Method for the treatment of glaucoma |
DE69227458T2 (de) | 1991-06-21 | 1999-04-29 | Smithkline Beecham Plc | Tryptamin analoga, ihre herstellung und anwendung als 5-ht1-artige rezeptoren oder 5-ht2 rezeptor agonisten |
IT1249678B (it) | 1991-07-12 | 1995-03-09 | Ciro Costagliola | Collirio per il trattamento della ipertensione oculare |
GB9216380D0 (en) * | 1992-07-31 | 1992-09-16 | Glaxo Group Ltd | Medicaments |
US5290781A (en) | 1993-01-05 | 1994-03-01 | Iolab Corporation | Ketaneserinol as an agent to reduce intraocular pressure |
EP0620222A3 (de) | 1993-04-14 | 1995-04-12 | Lilly Co Eli | Tetrahydro-betacarboline. |
TW334423B (en) | 1993-10-22 | 1998-06-21 | Hoffmann La Roche | Tricyclic 1-aminoethylpyrrole-derivatives |
TW270114B (de) | 1993-10-22 | 1996-02-11 | Hoffmann La Roche | |
US5538974A (en) | 1994-01-27 | 1996-07-23 | Senju Pharamceutical Co., Ltd. | Ophthalmic composition for lowering intraocular pressure |
ATE166227T1 (de) | 1994-03-18 | 1998-06-15 | Senju Pharma Co | Sarpogrelat enthaltende opthalmologische zubereitungen zur senkung des intraokularen druckes |
WO1996029074A1 (en) | 1995-03-22 | 1996-09-26 | Eli Lilly And Company | Methods of treating or preventing pain or nociception |
US5998467A (en) | 1995-10-25 | 1999-12-07 | Mitsubishi Chemical Corporation | Medicine for oculopathy |
US5696166A (en) * | 1995-10-31 | 1997-12-09 | Yanni; John M. | Compositions containing hydroxyeicosatetraenoic acid derivatives and methods of use in treating dry eye disorders |
RU2167160C2 (ru) | 1995-11-09 | 2001-05-20 | Санофи-Синтелябо | Производные 5-фенил-3-(пиперидин-4-ил)-1,3,4-оксадиазол-2(3н)-она, способ их получения, фармацевтическая композиция на их основе и лекарственное средство |
WO1997033579A1 (en) | 1996-03-13 | 1997-09-18 | Glaxo Group Limited | Medicaments comprising 5ht1-like receptor agonists with an increased absorption |
DE69710258T2 (de) * | 1996-06-17 | 2002-08-22 | Mitsubishi Chem Corp | Mittel zur Beschleunigung des Tränenflusses enthaltend einen Serotonin-Liganden, insbesondere Aminoalkoxybibenzyle |
WO1998018458A1 (en) * | 1996-10-31 | 1998-05-07 | Alcon Laboratories, Inc. | Opthalmological compositions containing serotonin 5-ht1a receptor agonist and their use in the treatment of glaucoma |
ATE257470T1 (de) | 1997-01-08 | 2004-01-15 | Hoffmann La Roche | Tricyclische benz(e)isoindole und benz(h)isochinoline |
AU5343298A (en) | 1997-01-13 | 1998-08-03 | Yamanouchi Pharmaceutical Co., Ltd. | 5-ht2c receptor agonists and aminoalkylindazole derivatives |
GB9700899D0 (en) | 1997-01-17 | 1997-03-05 | Smithkline Beecham Plc | Novel treatment |
EP0863136B1 (de) | 1997-02-25 | 2003-09-24 | Akzo Nobel N.V. | Azetidin- und Pyrrolidinderivate |
AU727654B2 (en) | 1997-06-13 | 2000-12-21 | Yamanouchi Pharmaceutical Co., Ltd. | Tricyclic pyrazole derivative |
GB9718833D0 (en) | 1997-09-04 | 1997-11-12 | Merck Sharp & Dohme | Therapeutic agents |
-
1999
- 1999-09-03 US US09/787,332 patent/US6664286B1/en not_active Expired - Lifetime
- 1999-09-03 ES ES99948085T patent/ES2252978T3/es not_active Expired - Lifetime
- 1999-09-03 WO PCT/US1999/019888 patent/WO2000016761A2/en not_active Application Discontinuation
- 1999-09-03 JP JP2000573722A patent/JP2002526443A/ja active Pending
- 1999-09-03 DK DK99948085T patent/DK1112106T3/da active
- 1999-09-03 CN CNB99810891XA patent/CN1269484C/zh not_active Expired - Fee Related
- 1999-09-03 CA CA002344150A patent/CA2344150A1/en not_active Abandoned
- 1999-09-03 AT AT99948085T patent/ATE310566T1/de not_active IP Right Cessation
- 1999-09-03 AU AU61326/99A patent/AU755119B2/en not_active Ceased
- 1999-09-03 BR BR9913800-0A patent/BR9913800A/pt not_active Application Discontinuation
- 1999-09-03 DE DE69928542T patent/DE69928542T2/de not_active Expired - Fee Related
- 1999-09-03 KR KR1020017003191A patent/KR20010073153A/ko not_active Application Discontinuation
- 1999-09-03 EP EP99948085A patent/EP1112106B1/de not_active Expired - Lifetime
- 1999-09-03 TR TR2001/00754T patent/TR200100754T2/xx unknown
- 1999-09-14 AR ARP990104608A patent/AR020442A1/es unknown
- 1999-09-17 TW TW088116092A patent/TWI229602B/zh not_active IP Right Cessation
-
2001
- 2001-03-15 ZA ZA200102157A patent/ZA200102157B/en unknown
- 2001-12-15 HK HK01108810A patent/HK1038516A1/xx not_active IP Right Cessation
-
2003
- 2003-05-09 US US10/434,708 patent/US20030203912A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
ES2252978T3 (es) | 2006-05-16 |
TWI229602B (en) | 2005-03-21 |
EP1112106B1 (de) | 2005-11-23 |
ATE310566T1 (de) | 2005-12-15 |
DE69928542D1 (de) | 2005-12-29 |
DE69928542T2 (de) | 2006-03-30 |
CA2344150A1 (en) | 2000-03-30 |
EP1112106A2 (de) | 2001-07-04 |
AU755119B2 (en) | 2002-12-05 |
TR200100754T2 (tr) | 2001-10-22 |
US6664286B1 (en) | 2003-12-16 |
BR9913800A (pt) | 2001-05-29 |
WO2000016761A2 (en) | 2000-03-30 |
AR020442A1 (es) | 2002-05-15 |
KR20010073153A (ko) | 2001-07-31 |
DK1112106T3 (da) | 2005-12-12 |
AU6132699A (en) | 2000-04-10 |
HK1038516A1 (en) | 2002-03-22 |
CN1317979A (zh) | 2001-10-17 |
JP2002526443A (ja) | 2002-08-20 |
WO2000016761A3 (en) | 2000-05-25 |
US20030203912A1 (en) | 2003-10-30 |
CN1269484C (zh) | 2006-08-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6664286B1 (en) | Serotonergic 5ht2 agonists for treating glaucoma | |
US6441047B2 (en) | Combination therapy for treating glaucoma | |
US6660870B1 (en) | 2-acylaminobenzimidazole derivatives for treating glaucoma | |
CA2400637A1 (en) | Compounds with 5-ht2 and 5-ht1a agonist activity for treating glaucoma | |
CN102711771B (zh) | 降低眼压的组合、试剂盒和方法 | |
JP2002521332A (ja) | 高眼圧治療用眼薬組成物 | |
WO2000054810A1 (en) | Combination therapy for treating glaucoma | |
WO1998018458A1 (en) | Opthalmological compositions containing serotonin 5-ht1a receptor agonist and their use in the treatment of glaucoma | |
US7005448B2 (en) | Aminoalkyl-benzofuran-5-ol compounds for the treatment of glaucoma | |
JP2003523976A (ja) | 眼圧降下脂質 | |
EP1268482B1 (de) | Pyranoindole zur glaukombehandlung | |
JP2005513103A (ja) | 緑内障の処置のための新規ベンゾジフランイミダゾリンおよびベンゾフランイミダゾリン誘導体ならびにそれらの使用 | |
US20060211700A1 (en) | (R)-8,9-dichloro-2,3,4,4a-tetrahydro-1H,6H-pyrazino[1,2-a]quinoxalin-5-one for controlling IOP and treating glaucoma | |
US7012090B1 (en) | Pyranoindoles for treating glaucoma | |
MXPA01002697A (en) | Serotonergic 5ht2 | |
US20030114512A1 (en) | Compounds with 5-ht2 and 5-ht1a agonist activity for treating glaucoma | |
AU2004214563A1 (en) | Combination therapy for treating glaucoma |