Dismukes K, Mulder A H
Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(1):23-9. doi: 10.1007/BF00508806.
The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1 - 1 micronM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect. The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM apomorphine. Apomorphine itself had no significant effect on 3H-DA release. Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS.
分析了电刺激纹状体切片释放3H-多巴胺的特性，并在不同实验条件下研究了多种抗精神病药物对其的影响。丁酰苯类药物氟哌啶醇和螺哌啶醇，即使在低浓度（0.1 - 1微摩尔）时也能以剂量依赖的方式增加基础氚外流。在这方面，吩噻嗪类药物氯丙嗪和氟奋乃静的效果要差得多。丁酰苯类药物强烈抑制电刺激引起的3H-多巴胺和14C-γ-氨基丁酸的溢出，而吩噻嗪类药物再次几乎没有作用。1微摩尔氟哌啶醇对3H-多巴胺释放的作用可被10微摩尔可卡因阻断，但不能被1微摩尔阿扑吗啡阻断。阿扑吗啡本身对3H-多巴胺释放没有显著影响。我们的数据不支持多巴胺能神经末梢上的突触前多巴胺受体可能调节新摄取的3H-多巴胺释放的观点。一些抗精神病药物，特别是丁酰苯类药物，可能具有与多巴胺受体相互作用无关的突触前效应。有人提出，中枢神经系统中去甲肾上腺素能和多巴胺能系统中递质释放的局部突触前受体介导的反馈调节可能涉及不同的机制。
