Preziosi P, Nisticò G
Int J Clin Pharmacol Biopharm. 1977 Nov;15(11):497-518.
Although the intimate mechanism by which psychotropic agents exert their therapeutic effects is still not completely clear, a large bulk of evidence supports the existence of a close correlation between their clinical antipsychotic acitivity and the ability to affect by different mechanisms brain monoamines and/or other real or putative neurotransmitters. Neuroleptic drugs of the phenothiazine type and related classes possess a blocking effect on dopaminergic transmission in nigro-striatal, mesolimbic and mesocortical areas; experiments supporting both a pre-and post-synaptic site of action have been described, together with the interference at the molecular level with DA-sensitive adenylate cyclase activity. In addition, anticholinergic activity and increase in GABA turnover in the striatum have been given as evidence to explain for some neuroleptics (e.g sulpiride, clozapine) lack of extrapyramidal side-effects. Anxiolytics seem to produce their therapeutic effect through a decrease in catecholaminegic and serotoninergic turnover although new avenues have been opened by some recent reports indicating a facilitation of GABAergic and glycinergic transmission in CNS.
尽管精神药物发挥其治疗作用的具体机制仍不完全清楚,但大量证据支持其临床抗精神病活性与通过不同机制影响脑单胺和/或其他实际或假定神经递质的能力之间存在密切相关性。吩噻嗪类及相关类别的抗精神病药物对黑质-纹状体、中脑边缘和中脑皮质区域的多巴胺能传递具有阻断作用;已经描述了支持突触前和突触后作用位点的实验,以及在分子水平上对多巴胺敏感的腺苷酸环化酶活性的干扰。此外,抗胆碱能活性和纹状体中γ-氨基丁酸(GABA)周转率的增加被作为解释某些抗精神病药物(如舒必利、氯氮平)缺乏锥体外系副作用的证据。抗焦虑药似乎通过降低儿茶酚胺能和5-羟色胺能的周转率产生治疗作用,尽管最近的一些报告开辟了新的途径,表明中枢神经系统中γ-氨基丁酸能和甘氨酸能传递得到促进。