Srivastava S K, Nath C
Department of Pharmacology, Pramukhswami Medical College, Karamsad, Gujarat, 388325, India.
Pharmacol Res. 2000 Oct;42(4):293-7. doi: 10.1006/phrs.2000.0696.
Various studies have shown that calcium channel blockers (CCB) affect the release of central neurotransmitters including noradrenaline (NA) and 5-hydroxytryptamine (5-HT), which are involved in depression. The behavioural despair test was used to investigate the effect of CCB on depression. The mice were treated acutely with CCB. Verapamil (5, 10, 20, and 40 mgkg(-1), i.p.) and diltiazem (10, 20, and 40 mgkg(-1), i.p.) produced a dose-dependent increase in immobility time, indicating the facilitation of depression, while nifedipine (12.5, 25, and 50 mgkg(-1), i.p.) significantly decreased the immobility time, indicating an antidepressant activity. Verapamil ( 40 mgkg(-1), i.p.) and diltiazem ( 40 mgkg(-1), i.p.) blocked the antidepressant effect of desipramine, clomipramine, mianserin, and tranylcypromine, indicating the involvement of various mechanisms in the facilitatory effect of verapamil and diltiazem on depression. The antidepressant effect of nifedipine may be attributed to the blockade of presynaptic alpha -2-receptors (autoreceptors), as nifedipine blocked the clonidine-induced facilitation of depression.
多项研究表明,钙通道阻滞剂(CCB)会影响包括去甲肾上腺素(NA)和5-羟色胺(5-HT)在内的中枢神经递质的释放,而这些神经递质与抑郁症有关。采用行为绝望试验来研究CCB对抑郁症的影响。小鼠接受CCB急性治疗。维拉帕米(5、10、20和40mg/kg(-1),腹腔注射)和地尔硫䓬(10、20和40mg/kg(-1),腹腔注射)使不动时间呈剂量依赖性增加,表明促进了抑郁,而硝苯地平(12.5、25和50mg/kg(-1),腹腔注射)显著缩短了不动时间,表明具有抗抑郁活性。维拉帕米(40mg/kg(-1),腹腔注射)和地尔硫䓬(40mg/kg(-1),腹腔注射)阻断了地昔帕明、氯米帕明、米安色林和反苯环丙胺的抗抑郁作用,表明维拉帕米和地尔硫䓬对抑郁症的促进作用涉及多种机制。硝苯地平的抗抑郁作用可能归因于对突触前α-2受体(自身受体)的阻断,因为硝苯地平阻断了可乐定诱导的抑郁促进作用。