Wang R Y, Ashby C R, Edwards E, Zhang J Y
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8790.
J Clin Psychiatry. 1994 Sep;55 Suppl B:23-6.
The serotonin3 (5-HT3)-like receptors play an important role in modulating the inhibitory action of dopamine in the mesocorticolimbic regions. The atypical antipsychotic drugs clozapine and RMI 81,582, but not other antipsychotic drugs, blocked the suppressant action produced by the 5-HT3 receptor agonist 2-methyl-5-HT on the firing rate of medial prefrontal cortical cells. Since the localization of 5-HT3 receptors overlaps with the mesocorticolimbic but not the nigrostriatal dopamine system, it is hypothesized that the preferential action of clozapine on the mesocorticolimbic dopamine system is the result of the drug's interaction with the 5-HT3-like receptors. Furthermore, the antagonizing effect of clozapine to 5-HT3-like receptors may contribute to its increased antipsychotic efficacy.
5-羟色胺3（5-HT3）样受体在调节中脑皮质边缘系统区域多巴胺的抑制作用中发挥重要作用。非典型抗精神病药物氯氮平和RMI 81,582能阻断5-HT3受体激动剂2-甲基-5-HT对内侧前额叶皮质细胞放电率产生的抑制作用，但其他抗精神病药物则不能。由于5-HT3受体的定位与中脑皮质边缘多巴胺系统重叠，而与黑质纹状体多巴胺系统不重叠，因此推测氯氮平对中脑皮质边缘多巴胺系统的优先作用是该药物与5-HT3样受体相互作用的结果。此外，氯氮平对5-HT3样受体的拮抗作用可能有助于其增强抗精神病疗效。
