McMillen B A, Mattiace L A
J Neural Transm. 1983;57(4):255-65. doi: 10.1007/BF01248997.
Buspirone is a clinically efficacious anti-anxiety drug without any other benzodiazepine-like activity. Although buspirone can displace ligands for dopamine (DA) receptors, its equipotent analog, MJ-13805, cannot. Buspirone can potently increase dopaminergic impulse flow and metabolism, primarily due to inhibition of DA autoreceptors. However, MJ-13805 does not block striatal nerve ending DA autoreceptors and slightly increases striatal DA metabolism. Both drugs potently reverse catalepsy due to either DA receptor blockade or DA depletion which indicates an effect within the extrapyramidal system efferent from the DA neuron. Amantadine is at least ten fold less potent than these drugs for reversal of catalepsy. These data indicate that altered dopaminergic neurotransmission may not be important for the anti-anxiety effect of buspirone and that buspirone should be tested for efficacy in various models of movement disorders. The site and mechanism of action for buspirone and MJ-13805 remains obscure. A metabolite of buspirone, 1-piperazinylpyrimidine, does not reverse catalepsy although this drug is known to be active in anti-anxiety screening tests. Thus, buspirone may have separate mechanisms of action for reduction of anxiety and reversal of catalepsy.
丁螺环酮是一种临床有效的抗焦虑药物，没有任何其他类似苯二氮䓬的活性。虽然丁螺环酮可以取代多巴胺（DA）受体的配体，但其等效类似物MJ-13805却不能。丁螺环酮可以显著增加多巴胺能冲动流量和代谢，主要是由于对DA自身受体的抑制。然而，MJ-13805并不阻断纹状体神经末梢DA自身受体，且只会轻微增加纹状体DA代谢。这两种药物都能有效逆转因DA受体阻断或DA耗竭引起的僵住症，这表明在DA神经元传出的锥体外系中有作用。金刚烷胺逆转僵住症的效力至少比这些药物低十倍。这些数据表明，多巴胺能神经传递的改变可能对丁螺环酮的抗焦虑作用并不重要，并且丁螺环酮应该在各种运动障碍模型中进行疗效测试。丁螺环酮和MJ-13805的作用部位和机制仍不清楚。丁螺环酮的一种代谢产物1-哌嗪基嘧啶不能逆转僵住症，尽管已知这种药物在抗焦虑筛选试验中具有活性。因此，丁螺环酮在减轻焦虑和逆转僵住症方面可能有不同的作用机制。
