JP2005516911A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2005516911A5 JP2005516911A5 JP2003550756A JP2003550756A JP2005516911A5 JP 2005516911 A5 JP2005516911 A5 JP 2005516911A5 JP 2003550756 A JP2003550756 A JP 2003550756A JP 2003550756 A JP2003550756 A JP 2003550756A JP 2005516911 A5 JP2005516911 A5 JP 2005516911A5
- Authority
- JP
- Japan
- Prior art keywords
- pramipexole
- mpp
- composition
- caspase
- ppx
- 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.)
- Granted
Links
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 claims description 45
- 229960003089 pramipexole Drugs 0.000 claims description 37
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 19
- FASDKYOPVNHBLU-UHFFFAOYSA-N N6-Propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine Chemical compound C1C(NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-UHFFFAOYSA-N 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 238000001361 intraarterial administration Methods 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000007912 intraperitoneal administration Methods 0.000 claims description 2
- 238000007913 intrathecal administration Methods 0.000 claims description 2
- 238000007914 intraventricular administration Methods 0.000 claims description 2
- 239000004090 neuroprotective agent Substances 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 29
- 230000000694 effects Effects 0.000 description 25
- 230000036542 oxidative stress Effects 0.000 description 20
- GLDQAMYCGOIJDV-UHFFFAOYSA-N Pyrocatechuic acid Natural products OC(=O)C1=CC=CC(O)=C1O GLDQAMYCGOIJDV-UHFFFAOYSA-N 0.000 description 17
- 230000004913 activation Effects 0.000 description 16
- 108090000397 Caspase 3 Proteins 0.000 description 15
- 102100029855 Caspase-3 Human genes 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 14
- 108010076667 Caspases Proteins 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 102000011727 Caspases Human genes 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 10
- ALUQMCBDQKDRAK-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazole Chemical compound C1C=CC=C2SCNC21 ALUQMCBDQKDRAK-UHFFFAOYSA-N 0.000 description 9
- 102000004039 Caspase-9 Human genes 0.000 description 9
- 108090000566 Caspase-9 Proteins 0.000 description 9
- BBFQZRXNYIEMAW-UHFFFAOYSA-N aristolochic acid I Chemical compound C1=C([N+]([O-])=O)C2=C(C(O)=O)C=C3OCOC3=C2C2=C1C(OC)=CC=C2 BBFQZRXNYIEMAW-UHFFFAOYSA-N 0.000 description 9
- 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 8
- 102000018832 Cytochromes Human genes 0.000 description 8
- 108010052832 Cytochromes Proteins 0.000 description 8
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical group O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 229960002378 oftasceine Drugs 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000030833 cell death Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000004770 neurodegeneration Effects 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 238000001374 small-angle light scattering Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 6
- 229960001860 salicylate Drugs 0.000 description 6
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 208000029028 brain injury Diseases 0.000 description 5
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 5
- -1 for example Chemical group 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 210000002161 motor neuron Anatomy 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 230000016273 neuron death Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- FASDKYOPVNHBLU-SSDOTTSWSA-N dexpramipexole Chemical compound C1[C@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-SSDOTTSWSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000003470 mitochondria Anatomy 0.000 description 4
- 230000002438 mitochondrial effect Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108020005196 Mitochondrial DNA Proteins 0.000 description 3
- 208000028389 Nerve injury Diseases 0.000 description 3
- 101710138657 Neurotoxin Proteins 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000008764 nerve damage Effects 0.000 description 3
- 239000002581 neurotoxin Substances 0.000 description 3
- 231100000618 neurotoxin Toxicity 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 231100000041 toxicology testing Toxicity 0.000 description 3
- 101710103970 ADP,ATP carrier protein Proteins 0.000 description 2
- 101710133192 ADP,ATP carrier protein, mitochondrial Proteins 0.000 description 2
- 208000035657 Abasia Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 210000002226 anterior horn cell Anatomy 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 230000003492 excitotoxic effect Effects 0.000 description 2
- 231100000063 excitotoxicity Toxicity 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000001690 micro-dialysis Methods 0.000 description 2
- 229940101972 mirapex Drugs 0.000 description 2
- 230000010021 mitochondrial pathology Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000004112 neuroprotection Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000004792 oxidative damage Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000002243 primary neuron Anatomy 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000004129 prosencephalon Anatomy 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- HLNJFEXZDGURGZ-UHFFFAOYSA-M 1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1 HLNJFEXZDGURGZ-UHFFFAOYSA-M 0.000 description 1
- WDJKAQCAPHSOIO-UHFFFAOYSA-N 1-phenyl-3,6-dihydro-2h-pyridine Chemical compound C1C=CCCN1C1=CC=CC=C1 WDJKAQCAPHSOIO-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- AUUIARVPJHGTSA-UHFFFAOYSA-N 3-(aminomethyl)chromen-2-one Chemical compound C1=CC=C2OC(=O)C(CN)=CC2=C1 AUUIARVPJHGTSA-UHFFFAOYSA-N 0.000 description 1
- RGOJCHYYBKMRLL-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(OC(F)(F)F)C=C1 RGOJCHYYBKMRLL-UHFFFAOYSA-N 0.000 description 1
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 229940123169 Caspase inhibitor Drugs 0.000 description 1
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 1
- 108090000365 Cytochrome-c oxidases Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010067671 Disease complication Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102100031562 Excitatory amino acid transporter 2 Human genes 0.000 description 1
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
- 229940123457 Free radical scavenger Drugs 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
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 101000866287 Homo sapiens Excitatory amino acid transporter 2 Proteins 0.000 description 1
- 238000003231 Lowry assay Methods 0.000 description 1
- 238000009013 Lowry's assay Methods 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- 108010067028 Mitochondrial Permeability Transition Pore Proteins 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108010014865 PLIalpha Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229940123898 Phospholipase A2 inhibitor Drugs 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000003149 assay kit Methods 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
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002038 chemiluminescence detection Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- QMNWXHSYPXQFSK-UHFFFAOYSA-N hydron;6-n-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;dichloride Chemical compound Cl.Cl.C1C(NCCC)CCC2=C1SC(N)=N2 QMNWXHSYPXQFSK-UHFFFAOYSA-N 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- SHCXABJSXUACKU-XTXDISFPSA-N isobongkrekic acid Natural products COC(CC=C/C=C/CCC=CCC(C)C=CC(=C/C(=O)O)CC(=O)O)C(=C/C=C(C)/C(=O)O)C SHCXABJSXUACKU-XTXDISFPSA-N 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 210000002311 liver mitochondria Anatomy 0.000 description 1
- 210000005230 lumbar spinal cord Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000001964 muscle biopsy Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003358 phospholipase A2 inhibitor Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002488 pyknotic effect Effects 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000010246 ultrastructural analysis Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33938301P | 2001-12-11 | 2001-12-11 | |
| US60/339,383 | 2001-12-11 | ||
| US34737102P | 2002-01-11 | 2002-01-11 | |
| US60/347,371 | 2002-01-11 | ||
| PCT/US2002/039970 WO2003049705A2 (en) | 2001-12-11 | 2002-12-02 | Use of pramipexole to treat amyotrophic lateral sclerosis |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009260955A Division JP2010031059A (ja) | 2001-12-11 | 2009-11-16 | 筋萎縮性側索硬化症を処置するためのプラミペキソールの使用 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2005516911A JP2005516911A (ja) | 2005-06-09 |
| JP2005516911A6 JP2005516911A6 (ja) | 2005-08-11 |
| JP2005516911A5 true JP2005516911A5 (https=) | 2010-01-21 |
| JP4500543B2 JP4500543B2 (ja) | 2010-07-14 |
Family
ID=26991607
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003550756A Expired - Lifetime JP4500543B2 (ja) | 2001-12-11 | 2002-12-02 | 筋萎縮性側索硬化症を処置するためのプラミペキソールの使用 |
| JP2009260955A Pending JP2010031059A (ja) | 2001-12-11 | 2009-11-16 | 筋萎縮性側索硬化症を処置するためのプラミペキソールの使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009260955A Pending JP2010031059A (ja) | 2001-12-11 | 2009-11-16 | 筋萎縮性側索硬化症を処置するためのプラミペキソールの使用 |
Country Status (19)
| Country | Link |
|---|---|
| US (4) | US7157480B2 (https=) |
| EP (4) | EP1453505B1 (https=) |
| JP (2) | JP4500543B2 (https=) |
| KR (1) | KR20040066890A (https=) |
| CN (1) | CN1617720A (https=) |
| AT (1) | ATE480235T1 (https=) |
| AU (1) | AU2002360600B2 (https=) |
| CA (1) | CA2468747C (https=) |
| CY (1) | CY1111237T1 (https=) |
| DE (1) | DE60237635D1 (https=) |
| DK (1) | DK1453505T3 (https=) |
| ES (2) | ES2432527T3 (https=) |
| HU (1) | HUP0500001A3 (https=) |
| IL (1) | IL162408A0 (https=) |
| MX (1) | MXPA04005572A (https=) |
| PL (1) | PL374310A1 (https=) |
| PT (1) | PT1453505E (https=) |
| RU (1) | RU2004121177A (https=) |
| WO (1) | WO2003049705A2 (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2432527T3 (es) * | 2001-12-11 | 2013-12-04 | University Of Virginia Patent Foundation | Uso de pramipexol para tratar la esclerosis lateral amiotrófica |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| ATE444750T1 (de) * | 2005-08-15 | 2009-10-15 | Univ Virginia | Neurorestauration mit r(+) pramipexol |
| EP1940398A1 (de) * | 2005-10-18 | 2008-07-09 | Boehringer Ingelheim International GmbH | Verwendung von pramipexol zur behandlung des moderaten bis schweren restless legs syndroms (rls) |
| US20070259930A1 (en) * | 2006-04-10 | 2007-11-08 | Knopp Neurosciences, Inc. | Compositions and methods of using r(+) pramipexole |
| US8518926B2 (en) * | 2006-04-10 | 2013-08-27 | Knopp Neurosciences, Inc. | Compositions and methods of using (R)-pramipexole |
| EP2465500A1 (en) * | 2006-05-16 | 2012-06-20 | Knopp Neurosciences, Inc. | Therapeutically effective amounts of R(+) and S(-) pramipexole for use in the treatment of parkinson's disease |
| ATE537826T1 (de) | 2006-05-16 | 2012-01-15 | Knopp Neurosciences Inc | Zusammensetzungen aus r(+)- und s(-)-pramipexol sowie verfahren zu ihrer anwendung |
| CN104107177A (zh) * | 2006-12-14 | 2014-10-22 | 诺普生物科学有限责任公司 | (r)-普拉克索的组合物以及使用该组合物的方法 |
| AU2013209376B2 (en) * | 2006-12-14 | 2016-05-05 | Knopp Biosciences Llc | Compositions and methods of using (r)-pramipexole |
| AU2016210640B2 (en) * | 2006-12-14 | 2018-02-22 | Knopp Biosciences Llc | Compositions and methods of using (r)-pramipexole |
| US8524695B2 (en) * | 2006-12-14 | 2013-09-03 | Knopp Neurosciences, Inc. | Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same |
| JP2010521496A (ja) | 2007-03-14 | 2010-06-24 | ノップ ニューロサイエンシーズ、インク． | キラル精製置換ベンゾチアゾールジアミンの合成 |
| EP2136638A4 (en) * | 2007-03-14 | 2010-05-12 | Knopp Neurosciences Inc | MODIFIED RELEASE FORMULATIONS OF (6R) -4,5,6,7-TETRAHYDRO-N6-PROPYL-2,6-BENZOTHIAZOLE DIAMINE AND METHODS OF USE THEREOF |
| GB0811642D0 (en) * | 2008-06-25 | 2008-07-30 | Univ Edinburgh | Assay |
| US20110190356A1 (en) * | 2008-08-19 | 2011-08-04 | Knopp Neurosciences Inc. | Compositions and Methods of Using (R)- Pramipexole |
| AU2010262970A1 (en) * | 2009-06-19 | 2012-01-12 | Knopp Neurosciences, Inc. | Compositions and methods for treating amyotrophic lateral sclerosis |
| WO2013096816A1 (en) | 2011-12-22 | 2013-06-27 | Biogen Idec Ma Inc. | Improved synthesis of amine substituted 4,5,6,7-tetrahydrobenzothiazole compounds |
| WO2014031883A1 (en) * | 2012-08-23 | 2014-02-27 | Susan Marie Metcalfe | Neurotherapeutic nanoparticle compositions and devices |
| US10874669B2 (en) | 2012-11-29 | 2020-12-29 | Wayne State University | Neuroprotective agents for treatment of neurodegenerative diseases |
| WO2014085600A1 (en) * | 2012-11-29 | 2014-06-05 | Wayne State University | Neuroprotective agents for treatment of neurodegenerative diseases |
| US9662313B2 (en) | 2013-02-28 | 2017-05-30 | Knopp Biosciences Llc | Compositions and methods for treating amyotrophic lateral sclerosis in responders |
| US9468630B2 (en) | 2013-07-12 | 2016-10-18 | Knopp Biosciences Llc | Compositions and methods for treating conditions related to increased eosinophils |
| PL3019167T3 (pl) | 2013-07-12 | 2021-06-14 | Knopp Biosciences Llc | Leczenie podwyższonych poziomów eozynofili i/lub bazofili |
| DK3033081T3 (da) | 2013-08-13 | 2021-05-31 | Knopp Biosciences Llc | Sammensætninger og fremgangsmåder til behandling af kronisk urticaria |
| EP3038467B1 (en) | 2013-08-13 | 2020-07-29 | Knopp Biosciences LLC | Compositions and methods for treating plasma cell disorders and b-cell prolymphocytic disorders |
| WO2019049145A1 (en) | 2017-09-11 | 2019-03-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | COMPOSITIONS AND METHODS FOR NASAL BRAIN MEDICATION ADMINISTRATION FOR SYSTEMIC EFFECT |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US560420A (en) | 1896-05-19 | Steam and oil separator | ||
| DE3447075A1 (de) * | 1984-12-22 | 1986-07-03 | Dr. Karl Thomae Gmbh, 7950 Biberach | Tetrahydro-benzthiazole, deren herstellung und deren verwendung als zwischenprodukte oder als arzneimittel |
| DE3572485D1 (en) | 1984-12-22 | 1989-09-28 | Thomae Gmbh Dr K | Tetrahydro-benzothiazoles, their production and their use as intermediates or drugs |
| DE3937271A1 (de) | 1989-11-09 | 1991-05-16 | Boehringer Ingelheim Kg | Transdermale applikation von 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazol |
| FR2688138B1 (fr) * | 1992-03-06 | 1995-05-05 | Rhone Poulenc Rorer Sa | Application de l'amino-2 trifluoromethoxy-6 benzothiazole pour obtenir un medicament destine au traitement de la sclerose laterale amyotrophique. |
| US6156777A (en) | 1994-12-15 | 2000-12-05 | Pharmacia & Upjohn Company | Use of pramipexole as a neuroprotective agent |
| US5650420A (en) * | 1994-12-15 | 1997-07-22 | Pharmacia & Upjohn Company | Pramipexole as a neuroprotective agent |
| ES2159362T3 (es) * | 1995-10-26 | 2001-10-01 | Sanofi Synthelabo | Utilizacion de la 1-(2-naft-2-iletil)-4-(3-trifluorometilfenil)-1,2,3,6-tetrahidropiridina para la preparacion de medicamentos destinados para el tratamiento de la esclerosis lateral amiotrofica. |
| GB9705428D0 (en) | 1997-03-15 | 1997-04-30 | Knoll Ag | Therapeutic agents |
| US6197339B1 (en) * | 1997-09-30 | 2001-03-06 | Pharmacia & Upjohn Company | Sustained release tablet formulation to treat Parkinson's disease |
| PE20000728A1 (es) * | 1998-06-26 | 2000-08-21 | Cocensys Inc | Heterociclos 4-bencil piperidina alquilsulfoxido y su uso como antagonistas receptores subtipo-selectivo nmda |
| DE19830201A1 (de) * | 1998-07-07 | 2000-01-13 | Boehringer Ingelheim Pharma | Mittel mit antidepressiver Wirkung |
| CA2301899C (en) * | 1998-07-27 | 2008-11-18 | Boehringer Ingelheim Pharma Kg | Agent with an antidepressant activity |
| MXPA01004381A (es) * | 1998-11-02 | 2005-09-08 | Elan Corp Plc | Composicion de multiparticulado de liberacion modificada. |
| DE19938825A1 (de) | 1999-08-19 | 2001-04-26 | Boehringer Ingelheim Pharma | Wirkstoffkombination mit Clonidin |
| CA2384840A1 (en) | 1999-09-30 | 2001-04-05 | The General Hospital Corporation | Use of pramipexole as a treatment for cocaine craving |
| PE20011074A1 (es) | 2000-02-23 | 2001-10-04 | Upjohn Co | Uso de pramipexol en el tratamiento de trastornos de adiccion |
| AU7887501A (en) * | 2000-07-06 | 2002-01-21 | Us Gov Health & Human Serv | Tetrahydrobenzothiazole analogues as neuroprotective agents |
| DE10037619A1 (de) * | 2000-08-02 | 2002-02-14 | Daimler Chrysler Ag | Anordnung von Bedienelementen |
| ES2187249B1 (es) * | 2000-09-18 | 2004-09-16 | Synthon Bv | Procedimiento para la preparacion de 2-amino-6-(alquil)amino-4,5,6,7-tetrahidrobenzotiazoles. |
| US20020151526A1 (en) * | 2000-10-06 | 2002-10-17 | Gallop Mark A. | Bile-acid prodrugs of L-dopa and their use in the sustained treatment of parkinsonism |
| DE10137082A1 (de) * | 2001-07-28 | 2003-02-13 | Hexal Ag | Matrixkontrolliertes transdermales therapeutisches System zur Anwendung von Pramiprexol und Ropinirol |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| ES2432527T3 (es) * | 2001-12-11 | 2013-12-04 | University Of Virginia Patent Foundation | Uso de pramipexol para tratar la esclerosis lateral amiotrófica |
| AU2002316231A1 (en) * | 2002-02-19 | 2003-09-29 | Xenoport, Inc. | Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof |
| US20050226926A1 (en) * | 2002-07-25 | 2005-10-13 | Pfizer Inc | Sustained-release tablet composition of pramipexole |
| PT1610791E (pt) * | 2003-03-31 | 2011-05-23 | Titan Pharmaceuticals Inc | Dispositivo polim?rico implant?vel para liberta??o sustentada de agonista da dopamina |
| US7662987B2 (en) * | 2003-07-15 | 2010-02-16 | Xenoport, Inc. | Methods for synthesis of acyloxyalkyl compounds |
| CN101022788B (zh) * | 2004-08-13 | 2010-11-10 | 贝林格尔·英格海姆国际有限公司 | 包含普拉克索或其可药用盐的延长释放小球制剂、其制备方法及其用途 |
| TW200616604A (en) * | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
| ATE444750T1 (de) * | 2005-08-15 | 2009-10-15 | Univ Virginia | Neurorestauration mit r(+) pramipexol |
-
2002
- 2002-12-02 ES ES10008579T patent/ES2432527T3/es not_active Expired - Lifetime
- 2002-12-02 PL PL02374310A patent/PL374310A1/xx unknown
- 2002-12-02 JP JP2003550756A patent/JP4500543B2/ja not_active Expired - Lifetime
- 2002-12-02 HU HU0500001A patent/HUP0500001A3/hu unknown
- 2002-12-02 KR KR10-2004-7008931A patent/KR20040066890A/ko not_active Withdrawn
- 2002-12-02 AU AU2002360600A patent/AU2002360600B2/en not_active Expired
- 2002-12-02 EP EP02795869A patent/EP1453505B1/en not_active Expired - Lifetime
- 2002-12-02 AT AT02795869T patent/ATE480235T1/de active
- 2002-12-02 PT PT02795869T patent/PT1453505E/pt unknown
- 2002-12-02 EP EP10009931A patent/EP2305252A1/en not_active Ceased
- 2002-12-02 EP EP10075571A patent/EP2305253A1/en not_active Withdrawn
- 2002-12-02 DK DK02795869.3T patent/DK1453505T3/da active
- 2002-12-02 CA CA2468747A patent/CA2468747C/en not_active Expired - Lifetime
- 2002-12-02 MX MXPA04005572A patent/MXPA04005572A/es unknown
- 2002-12-02 IL IL16240802A patent/IL162408A0/xx unknown
- 2002-12-02 RU RU2004121177/14A patent/RU2004121177A/ru not_active Application Discontinuation
- 2002-12-02 ES ES02795869T patent/ES2351303T3/es not_active Expired - Lifetime
- 2002-12-02 WO PCT/US2002/039970 patent/WO2003049705A2/en not_active Ceased
- 2002-12-02 CN CNA028278259A patent/CN1617720A/zh active Pending
- 2002-12-02 DE DE60237635T patent/DE60237635D1/de not_active Expired - Lifetime
- 2002-12-02 EP EP10008579.4A patent/EP2246053B1/en not_active Expired - Lifetime
- 2002-12-02 US US10/496,714 patent/US7157480B2/en not_active Expired - Lifetime
-
2006
- 2006-12-21 US US11/614,528 patent/US20070105918A1/en not_active Abandoned
-
2009
- 2009-11-16 JP JP2009260955A patent/JP2010031059A/ja active Pending
-
2010
- 2010-12-08 CY CY20101101132T patent/CY1111237T1/el unknown
-
2011
- 2011-08-01 US US13/195,552 patent/US20110301210A1/en not_active Abandoned
-
2013
- 2013-02-26 US US13/777,603 patent/US20130172394A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2005516911A5 (https=) | ||
| JP4500543B2 (ja) | 筋萎縮性側索硬化症を処置するためのプラミペキソールの使用 | |
| JP2005516911A6 (ja) | 筋萎縮性側索硬化症を処置するためのプラミペキソールの使用 | |
| JP6488237B2 (ja) | 選択的ｎｏｘ−１インヒビターペプチドおよびそれらの使用 | |
| CN113164446A (zh) | 用于抑制和/或治疗代谢病和/或其临床病症的组合物和方法 | |
| US11517554B2 (en) | Method for preventing or treating Alzheimer's disease | |
| KR102029090B1 (ko) | O-사이클릭 피토스핑고신-1-포스페이트를 포함하는 파킨슨병의 예방 또는 치료용 조성물 | |
| US20250064775A1 (en) | Selective elimination of senescent cells by ferroptosis induction | |
| US20210085676A1 (en) | Treatment for age- and oxidative stress-associated muscle atrophy and weakness | |
| US20260021167A1 (en) | Compositions and methods for treating or preventing neurodegenerative diseases | |
| EP4370143B1 (en) | A pharmaceutical micronutrient composition for use in the treatment of depression | |
| WO2023097280A1 (en) | Inhibition of sterol response element binding proteins as a target for selective elimination of senescent cells | |
| ZA200404433B (en) | Use of pramipexole to treat amyotrophic lateral sclerosis. | |
| JP4734560B2 (ja) | キノン体若しくはキノン体前駆体の毒性に起因する障害に対する予防治療剤 | |
| HK1150153B (en) | Use of pramipexole to treat amyotrophic lateral sclerosis | |
| HK1156238A (en) | Use of pramipexole to treat amyotrophic lateral sclerosis | |
| HK1156239A (en) | Use of pramipexole to treat amyotrophic lateral sclerosis | |
| AU2008200886A1 (en) | Use of Pramipexole to Treat Amyotrophic Lateral Sclerosis | |
| WO2023037173A1 (en) | A pharmaceutical micronutrient composition for use to simultaneously improve nervous system function, cognitive ability and response to stressors | |
| JP2008543900A (ja) | 神経病理学的疾患の処置及び／又は予防のためのウロキナーゼ阻害剤の使用 |