Feigenbaum J J, Yanai J, Klawans H L
Int J Neurosci. 1983;18(3-4):205-10. doi: 10.3109/00207458308987364.
Though quipazine is widely regarded as a relatively pure serotonergic (5-HT) agonist and has been reported to have no dopamine (DA) agonist properties, it has produced stereotyped behavior (SB) associated with DA agonist arousal of striatal DA mechanisms. Since we observed a dose-related inhibition of quipazine induced stereotypy (QISB) by a centrally acting DA antagonist (haloperidol) that could not be mimicked by a central 5-HT receptor blocking agent (methysergide), it appeared likely that QISB is mediated by striatal DA mechanisms. This was further supported by our observing that QISB could be potentiated by a subthreshold dose of the central DA agonist apomorphine. In light of this, and the presence of abnormal movements seen concomitantly with QISB that are typically produced by intrastriatal injections of 5-HT agonists, it appears that QISB is a complex phenomenon. While QISB seems to be primarily due to the stimulation of DA mechanisms, the effect of quipazine on behavior appears to be a combined result of its effects on both DA and 5-HT mechanisms. Specifically, central striatal DA receptors appear to mediate QISB per se, while serotonergic mechanisms stimulated by quipazine inhibit its further development and produce extrapyramidal-like abnormal movements.
尽管喹哌嗪被广泛认为是一种相对纯粹的血清素能(5-羟色胺,5-HT)激动剂,且据报道不具有多巴胺(DA)激动剂特性,但它却引发了与纹状体DA机制的DA激动剂激发相关的刻板行为(SB)。由于我们观察到一种中枢作用的DA拮抗剂(氟哌啶醇)对喹哌嗪诱导的刻板行为(QISB)具有剂量相关的抑制作用,而这种作用无法被一种中枢5-HT受体阻断剂(麦角酰二乙胺,methysergide)模拟,所以看起来QISB可能是由纹状体DA机制介导的。我们观察到QISB可被阈下剂量的中枢DA激动剂阿扑吗啡增强,这进一步支持了上述观点。鉴于此,以及在QISB同时出现的异常运动与通常由纹状体内注射5-HT激动剂所产生的异常运动相似,看来QISB是一种复杂的现象。虽然QISB似乎主要是由于DA机制受到刺激,但喹哌嗪对行为的影响似乎是其对DA和5-HT机制的作用共同产生的结果。具体而言,中枢纹状体DA受体似乎介导了QISB本身,而喹哌嗪刺激的血清素能机制则抑制其进一步发展并产生锥体外系样的异常运动。