Bergman J, Madras B K, Spealman R D
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA.
J Pharmacol Exp Ther. 1991 Sep;258(3):910-7.
The behavioral effects of dopamine antagonists differing in affinity and selectivity at D1 and D2 dopamine receptors were compared in squirrel monkeys responding under a fixed-interval schedule of stimulus-shock termination. D1-selective antagonists included (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23390; its enantiomer (S)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23388; [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H - benzo(d)naphtho-(2,1-b)azepine], SCH 39166; (R)-7-bromo-8-hydroxyl-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine, R-SKF 83566; (R)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol, R-SKF 83692; 2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol, RS-SKF 83692. D2-selective antagonists included cis-N-(1-benzyl-2-methylpyrrolidine-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide, YM-09151-2, eticlopride, raclopride, haloperidol, risperidone, remoxipride, S-sulpiride and R-sulpiride; nonselective dopamine antagonists were S-butaclamol and chlorpromazine. Regardless of selectivity for D1 or D2 receptors, all drugs produced dose-related decreases in fixed-interval responding. A high degree of stereoselectivity was evident for both D1 antagonists (SCH 23390 and R-SKF 83692 more potent than, respectively, SCH 23388 and RS-SKF 83692) and D2 antagonists (S-sulpiride more potent than R-sulpiride). High doses of the D1 and D2 antagonists also reduced motor activity and impaired coordination in monkeys in the home cage after test sessions.(ABSTRACT TRUNCATED AT 250 WORDS)
在松鼠猴按照固定间隔刺激-电击终止程序做出反应的过程中，比较了对D1和D2多巴胺受体亲和力和选择性不同的多巴胺拮抗剂的行为效应。D1选择性拮抗剂包括（R）-（+）-8-氯-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇，SCH 23390；其对映体（S）-（+）-8-氯-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇，SCH 23388；[（-）-反式-6,7,7a,8,9,13b-六氢-3-氯-2-羟基-N-甲基-5H-苯并（d）萘并（2,1-b）氮杂卓]，SCH 39166；（R）-7-溴-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓，R-SKF 83566；（R）-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇，R-SKF 83692；2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇，RS-SKF 83692。D2选择性拮抗剂包括顺式-N-（1-苄基-2-甲基吡咯烷-3-基）-5-氯-2-甲氧基-4-甲基氨基苯甲酰胺，YM-09151-2，依托必利，雷氯必利，氟哌啶醇，利培酮，瑞莫必利，S-舒必利和R-舒必利；非选择性多巴胺拮抗剂是S-布他拉莫和氯丙嗪。无论对D1或D2受体的选择性如何，所有药物均使固定间隔反应呈剂量相关减少。D1拮抗剂（SCH 23390和R-SKF 83692分别比SCH 23388和RS-SKF 83692更有效）和D2拮抗剂（S-舒必利比R-舒必利更有效）均表现出高度的立体选择性。在测试 sessions后，高剂量的D1和D2拮抗剂还降低了家笼中猴子的运动活性并损害了其协调性。（摘要截短于250字）
