title: Effects of talipexole on motor behavior in normal and MPTP-treated common marmosets.
abstract: Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 0.5 mg/animal i.v. once or twice) to common marmosets induced persistent parkinsonian motor deficits. The postsynaptic dopamine D2 receptor agonist properties of talipexole (B-HT 920, 2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine), which is believed to be a dopamine autoreceptor agonist, were examined using normal and MPTP-treated marmosets and were compared to these properties of bromocriptine, a selective dopamine D2 receptor agonist. Talipexole (20-160 micrograms/kg i.p.) dose dependently increased motor activity and reversed the akinesia and incoordination of movement in MPTP-treated marmosets. In normal marmosets, higher doses of talipexole (80-160 micrograms/kg i.p.) produced a dose-dependent increase in motor activity, while the lowest dose (20 micrograms/kg i.p.) depressed this activity. These data for talipexole were very similar to those for bromocriptine. Talipexole had, however, several properties different from those of bromocriptine; it had a rapid onset of antiparkinsonian activity compared to bromocriptine; it had more than 25 times as much activity potency as bromocriptine; a dose of talipexole (80 micrograms/kg i.p.) sufficient to produce the activity did not induce emesis as strongly as an insufficient dose of bromocriptine (0.5 mg/kg i.p.). These results suggest that talipexole has postsynaptic dopamine D2 receptor agonist properties and that these properties of talipexole may be favorable in the treatment of Parkinson's disease.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagoshima University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Irifune
authors.forename: M
authors.initials: M
authors.lastname: Nomoto
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001971:Bromocriptine / Q000494:pharmacology; D002144:Callithrix; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism
chemical_list: D001381:Azepines; D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; C024763:talipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine