二氢吡啶类钙拮抗剂与吗啡对脑内生物胺的相互作用。

Interaction between dihydropyridine calcium antagonists and morphine on the brain biogenic amines.

Gaggi R, Roncada P, Gianni A M, Dall'olio R

Department of Pharmacology, University of Bologna, Italy.

Gen Pharmacol. 1994 Sep;25(5):923-9. doi: 10.1016/0306-3623(94)90097-3.

Abstract

Nifedipine, nimodipine or nisoldipine, were i.p. administered to normal, morphine treated or morphine abstinent rats in order to study their effects on brain biogenic amines and metabolites. 2. On various brain areas, the compounds studied decreased DOPAC and/or HVA levels, but increased 5-HIAA levels, leaving unchanged DA and 5-HT contents. 3. This suggested that DA turnover was decreased, whereas 5-HT turnover was increased, by inhibition of neuronal calcium influx. 4. Calcium antagonists: (a) further enhanced the effect of morphine on 5-HT turnover, which may involve an indirect inhibition of voltage sensitive calcium channels; (b) antagonized the effects of morphine on DA turnover, which are believed to be mediated by disinhibition of dopaminergic pathways. 5. The dihydropyridine calcium antagonists showed some differences in regional specificity and in profile of effects.

摘要

将硝苯地平、尼莫地平或尼索地平腹腔注射给正常大鼠、经吗啡处理的大鼠或吗啡戒断大鼠，以研究它们对脑内生物胺及其代谢产物的影响。2. 在各个脑区，所研究的化合物降低了3,4-二羟基苯乙酸（DOPAC）和/或高香草酸（HVA）水平，但提高了5-羟吲哚乙酸（5-HIAA）水平，而多巴胺（DA）和5-羟色胺（5-HT）含量未变。3. 这表明通过抑制神经元钙内流，多巴胺周转率降低，而5-羟色胺周转率提高。4. 钙拮抗剂：（a）进一步增强了吗啡对5-羟色胺周转率的作用，这可能涉及对电压敏感性钙通道的间接抑制；（b）拮抗了吗啡对多巴胺周转率的作用，据信这是由多巴胺能通路的去抑制介导的。5. 二氢吡啶类钙拮抗剂在区域特异性和效应谱方面表现出一些差异。