ES2235170T3 - Enantiomero r de n-propargil-1-aminoindano para su tratamiento de diversas enfermedades y mesilato, esilato y sulfato del mismo. - Google Patents
Enantiomero r de n-propargil-1-aminoindano para su tratamiento de diversas enfermedades y mesilato, esilato y sulfato del mismo.Info
- Publication number
- ES2235170T3 ES2235170T3 ES95903505T ES95903505T ES2235170T3 ES 2235170 T3 ES2235170 T3 ES 2235170T3 ES 95903505 T ES95903505 T ES 95903505T ES 95903505 T ES95903505 T ES 95903505T ES 2235170 T3 ES2235170 T3 ES 2235170T3
- Authority
- ES
- Spain
- Prior art keywords
- salt
- pai
- pharmaceutical composition
- aminoindane
- propargil
- 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
- 238000011282 treatment Methods 0.000 title claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 17
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 title description 12
- 201000010099 disease Diseases 0.000 title description 8
- 229950007655 esilate Drugs 0.000 title description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 title 1
- 229950002475 mesilate Drugs 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 80
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 43
- 230000006378 damage Effects 0.000 claims abstract description 22
- 206010012289 Dementia Diseases 0.000 claims abstract description 14
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 14
- 208000013403 hyperactivity Diseases 0.000 claims abstract description 11
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 11
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 11
- 208000035475 disorder Diseases 0.000 claims abstract description 9
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 88
- 210000004556 brain Anatomy 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 31
- 208000014674 injury Diseases 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 208000027418 Wounds and injury Diseases 0.000 claims description 19
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 17
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 17
- 230000003902 lesion Effects 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 210000001328 optic nerve Anatomy 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 17
- 206010019196 Head injury Diseases 0.000 claims description 13
- 230000002887 neurotoxic effect Effects 0.000 claims description 12
- 239000003981 vehicle Substances 0.000 claims description 12
- 229940123736 Decarboxylase inhibitor Drugs 0.000 claims description 10
- 239000003954 decarboxylase inhibitor Substances 0.000 claims description 10
- 231100000189 neurotoxic Toxicity 0.000 claims description 10
- 230000008733 trauma Effects 0.000 claims description 10
- 201000006474 Brain Ischemia Diseases 0.000 claims description 8
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 8
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 8
- 206010008118 cerebral infarction Diseases 0.000 claims description 8
- 229960004502 levodopa Drugs 0.000 claims description 8
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 7
- 208000026139 Memory disease Diseases 0.000 claims description 6
- 208000028389 Nerve injury Diseases 0.000 claims description 6
- 229960004205 carbidopa Drugs 0.000 claims description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 6
- 230000008764 nerve damage Effects 0.000 claims description 6
- 208000020431 spinal cord injury Diseases 0.000 claims description 6
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical group OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 claims description 5
- 229960000911 benserazide Drugs 0.000 claims description 5
- 208000017194 Affective disease Diseases 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 3
- 229960003920 cocaine Drugs 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- 210000000278 spinal cord Anatomy 0.000 claims description 3
- 229940102223 injectable solution Drugs 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 45
- 230000015654 memory Effects 0.000 abstract description 8
- 240000001546 Byrsonima crassifolia Species 0.000 abstract 1
- 208000019022 Mood disease Diseases 0.000 abstract 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 140
- 108010062431 Monoamine oxidase Proteins 0.000 description 140
- 230000000694 effects Effects 0.000 description 96
- 241000700159 Rattus Species 0.000 description 62
- 230000005764 inhibitory process Effects 0.000 description 56
- 150000001875 compounds Chemical class 0.000 description 46
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 40
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- 239000003112 inhibitor Substances 0.000 description 34
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 31
- 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 28
- 239000000243 solution Substances 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 229940079593 drug Drugs 0.000 description 22
- 239000003814 drug Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- 229960003638 dopamine Drugs 0.000 description 20
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 20
- XJEVHMGJSYVQBQ-SECBINFHSA-N (1r)-2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2[C@H](N)CCC2=C1 XJEVHMGJSYVQBQ-SECBINFHSA-N 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 19
- 238000007912 intraperitoneal administration Methods 0.000 description 19
- 206010021143 Hypoxia Diseases 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 229960003878 haloperidol Drugs 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- 229960003732 tyramine Drugs 0.000 description 17
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 16
- -1 mesylate salt Chemical class 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 229960003946 selegiline Drugs 0.000 description 15
- 230000006399 behavior Effects 0.000 description 14
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical group C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 206010002660 Anoxia Diseases 0.000 description 12
- 241000976983 Anoxia Species 0.000 description 12
- 206010010904 Convulsion Diseases 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000007953 anoxia Effects 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 210000005036 nerve Anatomy 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000008602 contraction Effects 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 230000003389 potentiating effect Effects 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical class C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 10
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 10
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 10
- 230000001154 acute effect Effects 0.000 description 10
- 230000002490 cerebral effect Effects 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 210000004185 liver Anatomy 0.000 description 10
- 241000700199 Cavia porcellus Species 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 9
- 229920000881 Modified starch Polymers 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 229940025084 amphetamine Drugs 0.000 description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 9
- 239000008108 microcrystalline cellulose Substances 0.000 description 9
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- 230000001684 chronic effect Effects 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 210000003405 ileum Anatomy 0.000 description 7
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 7
- 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 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 210000001638 cerebellum Anatomy 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 230000007954 hypoxia Effects 0.000 description 6
- 230000002427 irreversible effect Effects 0.000 description 6
- 230000037023 motor activity Effects 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 208000009132 Catalepsy Diseases 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 5
- 206010047853 Waxy flexibility Diseases 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 230000001773 anti-convulsant effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 5
- 230000002093 peripheral effect Effects 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000007916 tablet composition Substances 0.000 description 5
- 208000025962 Crush injury Diseases 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000001961 anticonvulsive agent Substances 0.000 description 4
- 229960003965 antiepileptics Drugs 0.000 description 4
- 238000009395 breeding Methods 0.000 description 4
- 230000001488 breeding effect Effects 0.000 description 4
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 4
- 210000001630 jejunum Anatomy 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 210000003625 skull Anatomy 0.000 description 4
- 229940023144 sodium glycolate Drugs 0.000 description 4
- 230000003595 spectral effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229940095064 tartrate Drugs 0.000 description 4
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010029350 Neurotoxicity Diseases 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 206010044221 Toxic encephalopathy Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000036982 action potential Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
- 229940077388 benzenesulfonate Drugs 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 210000005257 cortical tissue Anatomy 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 210000005064 dopaminergic neuron Anatomy 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 206010027175 memory impairment Diseases 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 230000007659 motor function Effects 0.000 description 3
- 230000000324 neuroprotective effect Effects 0.000 description 3
- 231100000228 neurotoxicity Toxicity 0.000 description 3
- 230000007135 neurotoxicity Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- 206010003591 Ataxia Diseases 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- NHTGHBARYWONDQ-JTQLQIEISA-N L-α-methyl-Tyrosine Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C=C1 NHTGHBARYWONDQ-JTQLQIEISA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000030768 Optic nerve injury Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 206010061334 Partial seizures Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940082992 antihypertensives mao inhibitors Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- 239000007963 capsule composition Substances 0.000 description 2
- 235000013351 cheese Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 230000001066 destructive effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000013038 irreversible inhibitor Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000004973 motor coordination Effects 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000002581 neurotoxin Substances 0.000 description 2
- 231100000618 neurotoxin Toxicity 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000011302 passive avoidance test Methods 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 230000002315 pressor effect Effects 0.000 description 2
- 230000000216 proconvulsive effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- MEZLKOACVSPNER-UHFFFAOYSA-N selegiline Chemical compound C#CCN(C)C(C)CC1=CC=CC=C1 MEZLKOACVSPNER-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000006190 sub-lingual tablet Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000005292 vacuum distillation Methods 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
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 1
- MEZLKOACVSPNER-LBPRGKRZSA-N (2s)-n-methyl-1-phenyl-n-prop-2-ynylpropan-2-amine Chemical group C#CCN(C)[C@@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-LBPRGKRZSA-N 0.000 description 1
- YYNWDKOKDLIANV-UHFFFAOYSA-N 1-(1-methylcyclohexa-2,4-dien-1-yl)-3,6-dihydro-2h-pyridine Chemical compound C1CC=CCN1C1(C)CC=CC=C1 YYNWDKOKDLIANV-UHFFFAOYSA-N 0.000 description 1
- WLJXUWKOEVKMGD-UHFFFAOYSA-N 1-chloro-2,3-dihydro-1h-indene Chemical compound C1=CC=C2C(Cl)CCC2=C1 WLJXUWKOEVKMGD-UHFFFAOYSA-N 0.000 description 1
- KOWJANGMTAZWDT-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin-1-ium;chloride Chemical compound Cl.C1N(C)CCC(C=2C=CC=CC=2)=C1 KOWJANGMTAZWDT-UHFFFAOYSA-N 0.000 description 1
- QIMGSZURBOTPMW-UHFFFAOYSA-N 2-methoxy-5-(2,3,4-trimethoxyphenyl)cyclohepta-2,4,6-trien-1-one Chemical compound COC1=C(OC)C(OC)=CC=C1C1=CC=C(OC)C(=O)C=C1 QIMGSZURBOTPMW-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000004031 Carboxy-Lyases Human genes 0.000 description 1
- 108090000489 Carboxy-Lyases Proteins 0.000 description 1
- FMGYKKMPNATWHP-UHFFFAOYSA-N Cyperquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=CC=C1 FMGYKKMPNATWHP-UHFFFAOYSA-N 0.000 description 1
- 206010011953 Decreased activity Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- WXNXCEHXYPACJF-ZETCQYMHSA-N N-acetyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(C)=O WXNXCEHXYPACJF-ZETCQYMHSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- BKRGVLQUQGGVSM-KBXCAEBGSA-N Revanil Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 BKRGVLQUQGGVSM-KBXCAEBGSA-N 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 206010062119 Sympathomimetic effect Diseases 0.000 description 1
- 231100000288 TD50 Toxicity 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 229960000669 acetylleucine Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940089206 anhydrous dextrose Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 230000002927 anti-mitotic effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 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
- 229940125717 barbiturate Drugs 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 238000011208 chromatographic data Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 208000028502 clonic seizure Diseases 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 1
- 229960004192 diphenoxylate Drugs 0.000 description 1
- 229940021019 disal Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000003483 hypokinetic effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960003587 lisuride Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000007787 long-term memory Effects 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- FQXXSQDCDRQNQE-UHFFFAOYSA-N markiertes Thebain Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(OC)C5=C4C23C1O5 FQXXSQDCDRQNQE-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 108010041420 microbial alkaline proteinase inhibitor Proteins 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- UOLUPBDKXZXUBM-UHFFFAOYSA-N n,n-bis(prop-2-ynyl)-2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N(CC#C)CC#C)CCC2=C1 UOLUPBDKXZXUBM-UHFFFAOYSA-N 0.000 description 1
- PJPLZHVJBIMXLJ-UHFFFAOYSA-N n,n-bis(prop-2-ynyl)-2,3-dihydro-1h-inden-1-amine;2,3-dihydroxybutanedioic acid Chemical compound OC(=O)C(O)C(O)C(O)=O.C1=CC=C2C(N(CC#C)CC#C)CCC2=C1 PJPLZHVJBIMXLJ-UHFFFAOYSA-N 0.000 description 1
- RPUFERHPLAVBJN-UHFFFAOYSA-N n,n-dihydroxy-1-phenylmethanamine Chemical compound ON(O)CC1=CC=CC=C1 RPUFERHPLAVBJN-UHFFFAOYSA-N 0.000 description 1
- CSVGVHNFFZWQJU-UHFFFAOYSA-N n-methyl-n-prop-2-ynyl-2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N(CC#C)C)CCC2=C1 CSVGVHNFFZWQJU-UHFFFAOYSA-N 0.000 description 1
- CSVGVHNFFZWQJU-CYBMUJFWSA-N n-methyl-n-propargyl-1(r)-aminoindan Chemical compound C1=CC=C2[C@H](N(CC#C)C)CCC2=C1 CSVGVHNFFZWQJU-CYBMUJFWSA-N 0.000 description 1
- KAKOSJKZQFWHRT-UHFFFAOYSA-N n-prop-2-ynyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=CC=C2C(NCC#C)CCCC2=C1 KAKOSJKZQFWHRT-UHFFFAOYSA-N 0.000 description 1
- RUOKEQAAGRXIBM-UHFFFAOYSA-N n-prop-2-ynyl-2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(NCC#C)CCC2=C1 RUOKEQAAGRXIBM-UHFFFAOYSA-N 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000004776 neurological deficiency Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000001067 neuroprotector Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 231100001096 no neurotoxicity Toxicity 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 238000007833 oxidative deamination reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- NZVZJSIAQQZVIM-UHFFFAOYSA-N oxomethylideneplatinum Chemical compound O=C=[Pt] NZVZJSIAQQZVIM-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- LPNBBFKOUUSUDB-UHFFFAOYSA-M p-toluate Chemical compound CC1=CC=C(C([O-])=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-M 0.000 description 1
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 1
- 229960004851 pergolide Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000002135 phase contrast microscopy Methods 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000036584 pressor response Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- RAGBYXLIHQFIPK-UHFFFAOYSA-N prop-2-ynyl benzenesulfonate Chemical compound C#CCOS(=O)(=O)C1=CC=CC=C1 RAGBYXLIHQFIPK-UHFFFAOYSA-N 0.000 description 1
- OWAHJGWVERXJMI-UHFFFAOYSA-N prop-2-ynyl methanesulfonate Chemical compound CS(=O)(=O)OCC#C OWAHJGWVERXJMI-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000002310 reflectometry Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000033287 response to anoxia Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000001020 rhythmical effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 1
- 229930003945 thebaine Natural products 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229960003741 tranylcypromine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Fats And Perfumes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US139517 | 1987-12-30 | ||
| US13951793A | 1993-10-18 | 1993-10-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2235170T3 true ES2235170T3 (es) | 2005-07-01 |
Family
ID=22487049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES95903505T Expired - Lifetime ES2235170T3 (es) | 1993-10-18 | 1994-10-12 | Enantiomero r de n-propargil-1-aminoindano para su tratamiento de diversas enfermedades y mesilato, esilato y sulfato del mismo. |
Country Status (17)
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5744500A (en) | 1990-01-03 | 1998-04-28 | Teva Pharmaceutical Industries, Ltd. | Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof |
| US5844003A (en) * | 1991-04-04 | 1998-12-01 | Innovations Foundation | Use of deprenyl compounds to maintain, prevent loss, or recover nerve cell function |
| DE4327516A1 (de) * | 1993-08-17 | 1995-02-23 | Asta Medica Ag | Primäre und sekundäre neuroprotektive Wirkung bei neurodegenerativen Erkrankungen von Flupirtin |
| JP4782252B2 (ja) * | 1994-01-10 | 2011-09-28 | テバ ファーマシューティカル インダストリーズ リミテッド | １−アミノインダン及びこれらの組成物 |
| US5914349A (en) | 1994-01-10 | 1999-06-22 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
| US20010021722A1 (en) * | 1995-03-02 | 2001-09-13 | Mary Brewer Francesca | Pharmaceutical compositions comprising monoamine oxidase b inhibitors |
| CA2212412A1 (en) * | 1995-02-10 | 1996-08-15 | The University Of Toronto Innovations Foundation | Deprenyl compounds for treatment of glaucoma |
| IL115357A (en) * | 1995-09-20 | 2000-01-31 | Teva Pharma | Stable compositions containing N-propargyl-1-aminoindan and polyhydric alcohols |
| IL118836A (en) * | 1996-07-11 | 2001-01-11 | Teva Pharma | Pharmaceutical compositions comprising s-(-)-n-propargyl-1-aminoindan |
| IL119417A (en) * | 1996-10-13 | 2003-02-12 | Moshe Kushnir | Pharmaceutical composition for transdermal administration of levodopa for parkinson's disease |
| JP4222632B2 (ja) | 1996-12-18 | 2009-02-12 | テバ・ファーマシューティカル・インダストリーズ・リミテッド | アミノインダン誘導体 |
| GB9715082D0 (en) * | 1997-07-17 | 1997-09-24 | Scherer Ltd R P | Treatment of attention deficit hyperactivity disorder and narcolepsy |
| CA2319318A1 (en) * | 1998-01-27 | 1999-07-29 | Thomas N. Thomas | Methods of treatment using mao-a and mao-b inhibitors such as l-deprenyl |
| US6737547B1 (en) | 1998-12-31 | 2004-05-18 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using N-acyl-1H-aminoindenes |
| JP2003512426A (ja) | 1999-10-27 | 2003-04-02 | テバ ファーマシューティカル インダストリーズ リミティド | 双極性気分障害における躁病の治療のための１−アミノインダンの使用。 |
| ES2432117T3 (es) * | 2002-11-15 | 2013-11-29 | Teva Pharmaceutical Industries Limited | Uso de rasagilina con riluzol para tratar la esclerosis lateral amiotrófica |
| AR044007A1 (es) * | 2003-04-11 | 2005-08-24 | Newron Pharmaceuticals Inc | Metodos para el tratamiento de la enfermedad de parkinson |
| EP1588704A1 (en) * | 2004-04-22 | 2005-10-26 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful in the treatment of restless legs syndrome and addictive disorders |
| RU2404746C2 (ru) | 2005-02-23 | 2010-11-27 | Тева Фармасьютикал Индастриз, Лтд. | Композиции разагилина с улучшенной однородностью содержимого |
| EP1954667B1 (en) | 2005-11-17 | 2017-02-08 | Teva Pharmaceutical Industries Ltd | Methods for isolating propargylated aminoindans |
| US7572834B1 (en) | 2005-12-06 | 2009-08-11 | Teva Pharmaceutical Industries, Ltd. | Rasagiline formulations and processes for their preparation |
| AU2006326642B2 (en) | 2005-12-09 | 2012-05-03 | Technion Research And Development Foundation Ltd. | Use of low-dose ladostigil for neuroprotection |
| CA2643235C (en) * | 2006-02-21 | 2014-06-17 | Teva Pharmaceutical Industries, Ltd. | Use of rasagiline for the treatment of multiple system atrophy |
| TW200744576A (en) | 2006-02-24 | 2007-12-16 | Teva Pharma | Propargylated aminoindans, processes for preparation, and uses thereof |
| EP2007369A4 (en) * | 2006-04-03 | 2009-07-01 | Teva Pharma | USE OF RASAGILINE FOR THE TREATMENT OF LEG SYNDROME WITHOUT REST |
| EP1892233A1 (de) * | 2006-08-18 | 2008-02-27 | Ratiopharm GmbH | Neue Salze des Wirkstoffs Rasagilin |
| UA97382C2 (ru) | 2006-12-14 | 2012-02-10 | Тева Фармасьютікл Індастріз, Лтд. | Таннат разагилина |
| ATE528989T1 (de) | 2006-12-14 | 2011-11-15 | Teva Pharma | Kristalline feste rasagilin-base |
| CA2698695A1 (en) * | 2007-09-05 | 2009-03-12 | Teva Pharmaceutical Industries Ltd. | Method of treating glaucoma using rasagiline |
| AU2008339607B2 (en) | 2007-12-24 | 2012-08-02 | Cipla Limited | Process for the synthesis of propargylated aminoindan derivatives |
| US20110117200A1 (en) * | 2008-03-31 | 2011-05-19 | Actavis Group Ptc Ehf | Rasagiline mesylate particles and process for the preparation thereof |
| EP2303829A2 (en) | 2008-05-23 | 2011-04-06 | Medichem, S.A. | A new method for obtaining an aminoindan mesylate derivative |
| WO2009147430A1 (en) * | 2008-06-02 | 2009-12-10 | Generics [Uk] Limited | A process for the preparation of enantiomerically pure amines |
| CA2723870C (en) * | 2008-06-02 | 2015-04-21 | Generics [Uk] Limited | An improved process for the preparation of amines |
| WO2009154782A1 (en) * | 2008-06-19 | 2009-12-23 | Teva Pharmaceutical Industries, Ltd. | Process for purifying rasagiline base |
| US20100010098A1 (en) | 2008-07-11 | 2010-01-14 | Walter Elffrink | Polymorphs of rasagiline hydrochloride |
| WO2010007181A2 (en) * | 2008-07-18 | 2010-01-21 | Medichem, S.A. | New salt forms of an aminoindan derivative |
| DE102008064061A1 (de) | 2008-12-19 | 2010-06-24 | Ratiopharm Gmbh | Feste Zusammensetzung mit dem Wirkstoff Rasagilin |
| US8080584B2 (en) | 2009-01-23 | 2011-12-20 | Teva Pharmaceuticals Industries, Ltd. | Delayed release rasagiline citrate formulation |
| AU2010270254A1 (en) * | 2009-07-09 | 2012-02-02 | Ratiopharm Gmbh | Salts of rasagiline and pharmaceutical preparations thereof |
| CN102048717B (zh) † | 2009-10-29 | 2014-02-19 | 重庆医药工业研究院有限责任公司 | 一种稳定的雷沙吉兰组合物 |
| EP2325159A1 (en) | 2009-11-24 | 2011-05-25 | LEK Pharmaceuticals d.d. | Novel salts of rasagiline |
| MX2012007375A (es) | 2009-12-22 | 2012-07-30 | Teva Pharma | 3-ceto-n-propargil 1-aminoindano. |
| EP2519496A2 (en) * | 2009-12-30 | 2012-11-07 | Actavis Group Ptc Ehf | Solid state forms of rasagiline salts |
| RU2734632C2 (ru) | 2010-02-03 | 2020-10-21 | Фарма Ту Б Лтд. | Составы разагилина с пролонгированным высвобождением и их применение |
| WO2011121607A2 (en) | 2010-03-29 | 2011-10-06 | Cadila Healthcare Limited | Rasagiline and its pharmaceutically acceptable salts |
| EP2389927A1 (en) | 2010-05-30 | 2011-11-30 | Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi | Pharmaceutical formulations of rasagiline |
| CN102464589A (zh) * | 2010-11-17 | 2012-05-23 | 凯瑞斯德生化(苏州)有限公司 | 雷沙吉兰、其甲磺酸盐及其中间体的制备方法 |
| US8901352B2 (en) | 2011-01-13 | 2014-12-02 | Nobel Ilaç Sanayii Ve Ticaret A.S. | Method for the synthesis of rasagiline |
| WO2012116752A1 (en) | 2011-03-03 | 2012-09-07 | Synthon Bv | Process of resolution of 1-aminoindan |
| WO2012153349A2 (en) | 2011-05-04 | 2012-11-15 | Cadila Healthcare Limited | Rasagiline and its pharmaceutically acceptable salts |
| AU2012323349A1 (en) * | 2011-10-10 | 2014-05-22 | Teva Pharmaceutical Industries Ltd. | R(+)-N-formyl-propargyl-aminoindan |
| DE102012000786A1 (de) | 2012-01-18 | 2013-07-18 | Stada Arzneimittel Ag | Verfahren zur Herstellung einer festen pharmazeutischen Zusammensetzung, enthaltend den Wirkstoff Rasagilin |
| MX343986B (es) | 2012-03-21 | 2016-12-01 | Synthon Bv | Composiciones farmaceuticas estabilizadas que comprenden sales de rasagilina. |
| WO2013175493A1 (en) | 2012-04-09 | 2013-11-28 | Cadila Healthcare Limited | Stable oral pharmaceutical compositions |
| EP2764862A1 (en) * | 2013-02-06 | 2014-08-13 | Galenicum Health S.L. | Immediate release tablets of rasagiline hemitartrate |
| EP2796130A3 (en) | 2013-02-06 | 2015-02-25 | Galenicum Health S.L. | Immediate release tablets of rasagiline hemitartrate |
| IN2013MU01782A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 2013-05-20 | 2015-06-26 | Cadila Healthcare Ltd |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1187017A (en) * | 1966-07-16 | 1970-04-08 | Aspro Nicholas Ltd | Substituted 1-Amino Indanes and Tetrahydronaphthalens |
| DE3779500T2 (de) * | 1986-06-10 | 1993-01-21 | Chiesi Farma Spa | Levodopa-methyl-ester enthaltende pharmazeutische zusammensetzungen, ihre herstellung und therapeutische verwendungen. |
| IL92952A (en) * | 1990-01-03 | 1994-06-24 | Teva Pharma | R-enantiomers of n-propargyl-1-aminoindan compounds, their preparation and pharmaceutical compositions containing them |
| IL112819A (en) * | 1991-10-16 | 2001-11-25 | Teva Pharma | Fluorinated 1-aminoindan compounds and a process for their preparation |
-
1994
- 1994-10-11 IL IL11124094A patent/IL111240A/en not_active IP Right Cessation
- 1994-10-12 ES ES95903505T patent/ES2235170T3/es not_active Expired - Lifetime
- 1994-10-12 EP EP95903505A patent/EP0812190B1/en not_active Expired - Lifetime
- 1994-10-12 AU AU12534/95A patent/AU1253495A/en not_active Abandoned
- 1994-10-12 AT AT95903505T patent/ATE284208T1/de active
- 1994-10-12 JP JP7512014A patent/JPH09505806A/ja not_active Withdrawn
- 1994-10-12 HU HU9601012A patent/HU226138B1/hu active Protection Beyond IP Right Term
- 1994-10-12 DE DE69434178T patent/DE69434178T2/de not_active Expired - Lifetime
- 1994-10-12 DK DK95903505T patent/DK0812190T3/da active
- 1994-10-12 DE DE200512000044 patent/DE122005000044I2/de active Active
- 1994-10-12 PT PT95903505T patent/PT812190E/pt unknown
- 1994-10-12 WO PCT/US1994/011567 patent/WO1995011016A1/en active IP Right Grant
- 1994-10-12 CA CA002174449A patent/CA2174449C/en not_active Expired - Lifetime
- 1994-10-13 ZA ZA948013A patent/ZA948013B/xx unknown
- 1994-10-17 MX MXPA94008019A patent/MXPA94008019A/es active IP Right Grant
-
2002
- 2002-10-17 JP JP2002303097A patent/JP2003160481A/ja not_active Withdrawn
-
2005
- 2005-08-09 FR FR05C0033C patent/FR05C0033I2/fr active Active
- 2005-08-10 LU LU91191C patent/LU91191I2/fr unknown
- 2005-08-15 NL NL300205C patent/NL300205I2/nl unknown
-
2009
- 2009-09-24 JP JP2009219662A patent/JP2010018626A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010018626A (ja) | 2010-01-28 |
| IL111240A0 (en) | 1994-12-29 |
| MXPA94008019A (es) | 2004-08-10 |
| DE69434178T2 (de) | 2005-12-01 |
| EP0812190A1 (en) | 1997-12-17 |
| EP0812190B1 (en) | 2004-12-08 |
| HUT77934A (hu) | 1998-11-30 |
| LU91191I2 (fr) | 2005-10-10 |
| FR05C0033I1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2005-09-30 |
| NL300205I1 (nl) | 2005-10-03 |
| CA2174449C (en) | 2007-01-16 |
| HU226138B1 (en) | 2008-05-28 |
| NL300205I2 (nl) | 2006-03-01 |
| PT812190E (pt) | 2005-04-29 |
| CA2174449A1 (en) | 1995-04-27 |
| JPH09505806A (ja) | 1997-06-10 |
| AU1253495A (en) | 1995-05-08 |
| DK0812190T3 (da) | 2005-04-11 |
| JP2003160481A (ja) | 2003-06-03 |
| FR05C0033I2 (fr) | 2006-12-29 |
| EP0812190A4 (en) | 1998-03-04 |
| ATE284208T1 (de) | 2004-12-15 |
| DE69434178D1 (de) | 2005-01-13 |
| IL111240A (en) | 2001-10-31 |
| HU9601012D0 (en) | 1996-06-28 |
| ZA948013B (en) | 1995-05-31 |
| WO1995011016A1 (en) | 1995-04-27 |
| DE122005000044I1 (de) | 2005-12-22 |
| DE122005000044I2 (de) | 2007-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2235170T3 (es) | Enantiomero r de n-propargil-1-aminoindano para su tratamiento de diversas enfermedades y mesilato, esilato y sulfato del mismo. | |
| US5532415A (en) | R-enantiomer of N-propargyl-1-aminoindan, salts, compositions and uses thereof | |
| KR100412154B1 (ko) | N-프로파길-1-아미노인단의r-에난시오머,염,및그들의조성물의사용 |