SCH 23390 and its S-enantiomer stereoselectively prevent EEG and behavioral activation induced by dopamine agonists in the rabbit.
The selective D-1 dopamine antagonist SCH 23390 (R-enantiomer) and its unselective S-enantiomer (SCH 23388) were compared for their ability to prevent EEG and behavioral activation induced by the dopamine receptor agonists SKF 38393, apomorphine and LY 171555 in the rabbit. SCH 23390, at very low doses (0.003 mg/kg IV), inhibited EEG responses elicited by SKF 38393 and apomorphine, while the S-enantiomer displayed similar effects at doses at least 300-fold higher (1-3 mg/kg IV). Both isomers were approximately equipotent in preventing behavioral excitation caused by the D-2 agonist LY 171555. The dose of SCH 23390 interacting with LY 171555 was at least 100-fold higher than that effective for D-1 mediated responses. Conversely, the doses of S-enantiomer which prevented the stimulating effects induced by the different dopamine agonists were similar. The data demonstrate the stereoselectivity of the R-isomer SCH 23390 for blockade of D-1 receptors in vivo and provide evidence for the sensitivity of the EEG models in studying D-1 mediated responses.
Ongini
E
E
Caporali
M G
MG
Massotti
M
M
Sagratella
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D019257:Quinpirole; D011817:Rabbits; D011954:Receptors, Dopamine / Q000502:physiology*; D013237:Stereoisomerism
D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole