title: The D-1 dopamine receptor partial agonist, CY 208-243, exhibits antiparkinsonian activity in the MPTP-treated marmoset.
abstract: Administration of L-DOPA plus carbidopa, or the D-2 agonist (+)-PHNO, to MPTP-treated common marmosets caused motor hyperactivity and a reversal of the parkinsonian syndrome. In contrast, administration of the putative D-1 agonist SKF 38393 was without effect on movement or motor disability. The subsequent administration of another putative selective D-1 partial agonist CY 208-243 produced a dose-related improvement in motor activity and reversal of parkinsonian motor deficits in MPTP-treated animals. The effect of CY 208-243 was inhibited by pretreatment with the D-1 antagonist SCH 23390 and, to a lesser extent, by the D-2 antagonist sulpiride. In another group of normal drug naive marmosets, the administration of CY 208-243 produced only a small increase in motor activity. Following treatment with MPTP and without other drug administration, administration of CY 208-243 produced a marked reversal of motor deficits and locomotor hyperactivity. Thus, CY 208-243, suggested to be a partial D-1 agonist exhibits antiparkinsonian activity in MPTP-treated marmosets which does not require prior or concurrent exposure to D-2 agonists.
authors.affiliation: University Department of Neurology, National Hospital, London, U.K.
authors.forename: J A
authors.initials: JA
authors.lastname: Temlett
authors.forename: P N
authors.initials: PN
authors.lastname: Chong
authors.forename: W H
authors.initials: WH
authors.lastname: Oertel
authors.forename: P
authors.initials: P
authors.lastname: Jenner
authors.forename: C D
authors.initials: CD
authors.lastname: Marsden
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002143:Callitrichinae; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000517:prevention & control; D010617:Phenanthridines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D017447:Receptors, Dopamine D1; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D007211:Indoles; D010617:Phenanthridines; D011725:Pyridines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C054531:CY 208-243; D013469:Sulpiride; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine