Ongini E, Caporali M G, Massotti M, Sagratella S
Pharmacol Biochem Behav. 1987 Apr;26(4):715-8. doi: 10.1016/0091-3057(87)90602-2.
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.
比较了选择性D-1多巴胺拮抗剂SCH 23390（R-对映体）及其非选择性S-对映体（SCH 23388）预防多巴胺受体激动剂SKF 38393、阿扑吗啡和LY 171555诱导的兔脑电图（EEG）和行为激活的能力。极低剂量（0.003mg/kg静脉注射）的SCH 23390可抑制SKF 38393和阿扑吗啡引起的EEG反应，而S-对映体在至少高300倍的剂量（1-3mg/kg静脉注射）时才显示出类似作用。两种异构体在预防由D-2激动剂LY 171555引起的行为兴奋方面大致等效。与LY 171555相互作用的SCH 23390剂量比对D-1介导反应有效的剂量至少高100倍。相反，预防不同多巴胺激动剂诱导的刺激作用的S-对映体剂量相似。这些数据证明了R-异构体SCH 23390在体内阻断D-1受体的立体选择性，并为EEG模型在研究D-1介导反应中的敏感性提供了证据。
