Antiparkinsonian activity of talipexole in MPTP-treated monkeys: in combination with L-dopa and as chronic treatment.
We examined whether or not the antiparkinsonian activity of talipexole (B-HT 920, 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) could be optimised by combination with L-3,4-dihydroxyphenylalanine (L-dopa). Additionally, the effects of chronic treatment with talipexole on motor behavior were investigated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated and normal common marmosets. Administration of MPTP (0.5 mg/animal i.v. once or twice) to marmosets induced persistent parkinsonian motor deficits. The antiparkinsonian activity of talipexole (40 micrograms/kg s.c.) was significantly enhanced by its combination with L-dopa (30 mg/kg i.p.). This may further support the postulated postsynaptic dopamine D2 receptor agonist properties of talipexole. Chronic treatment with talipexole (a daily dose of 40 micrograms/kg s.c. for 21 days) did not lead to tolerance to the antiparkinsonian activity in MPTP-treated animals. No obvious dyskinesia was seen throughout the chronic treatment. In contrast, in normal marmosets, talipexole at a dose of 80 micrograms/kg which is a dose sufficient to induce hyperactivity did not increase motor activity during the treatment repeated for 21 days. These results suggest that talipexole is a selective dopamine D2 receptor agonist drug of potential use in the treatment of Parkinson's disease.
Department of Pharmacology, Faculty of Medicine, Kagoshima University, Japan.
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Irifune
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Nomoto
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Fukuda
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002144:Callithrix; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020267:MPTP Poisoning; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*
D000978:Antiparkinson Agents; D001381:Azepines; D018491:Dopamine Agonists; D007980:Levodopa; C024763:talipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine