The D-1 dopamine receptor partial agonist, CY 208-243, exhibits antiparkinsonian activity in the MPTP-treated marmoset.
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.
Temlett
J A
JA
University Department of Neurology, National Hospital, London, U.K.
Chong
P N
PN
Oertel
W H
WH
Jenner
P
P
Marsden
C D
CD
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
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