Chipkin R E, Latranyi M B
Eur J Pharmacol. 1987 Apr 29;136(3):371-5. doi: 10.1016/0014-2999(87)90310-4.
Clozapine at doses up to 100 mg/kg p.o. did not antagonize apomorphine-induced stereotypy in vehicle pre-treated rats. However, if the animals were injected with reserpine (30 mg/kg i.p.) 24 h prior to the test, then clozapine (3-100 mg/kg p.o.) produced a dose-related blockade of apomorphine-induced stereotypy. The blockade of apomorphine-induced stereotypy in reserpinized rats by clozapine was attenuated by the D-2 selective agonist LY 171555 but not the D-1 selective agonist SKF 38393. This profile of agonist reversal of antagonist blockade of apomorphine-induced stereotypy seen with clozapine was identical to that seen with the selective D-1 antagonist SCH 23390. Presumably, the D-2 agonist was active because D-1 receptor systems were inhibited (either at the receptor or at some other post-synaptic site) by clozapine or SCH 23390; this allowed a partial restoration of apomorphine-induced stereotypy via the D-2 system. Therefore, these data indicate that clozapine and SCH 23390 share a common mechanism of action via D-1 receptor systems.
剂量高达100毫克/千克口服的氯氮平，在预先用赋形剂处理的大鼠中，并未拮抗阿扑吗啡诱导的刻板行为。然而，如果在测试前24小时给动物注射利血平（30毫克/千克腹腔注射），那么氯氮平（3 - 100毫克/千克口服）会产生与剂量相关的对阿扑吗啡诱导刻板行为的阻断作用。氯氮平对利血平化大鼠中阿扑吗啡诱导刻板行为的阻断作用，被D - 2选择性激动剂LY 171555减弱，但未被D - 1选择性激动剂SKF 38393减弱。氯氮平所呈现的这种激动剂逆转拮抗剂对阿扑吗啡诱导刻板行为阻断作用的情况，与选择性D - 1拮抗剂SCH 23390所呈现的情况相同。据推测，D - 2激动剂之所以有活性，是因为D - 1受体系统被氯氮平或SCH 23390抑制（要么在受体处，要么在某些其他突触后位点）；这使得通过D - 2系统部分恢复了阿扑吗啡诱导的刻板行为。因此，这些数据表明氯氮平和SCH 23390通过D - 1受体系统具有共同的作用机制。
