Little H J, Dolin S J, Halsey M J
Life Sci. 1986 Dec 1;39(22):2059-65. doi: 10.1016/0024-3205(86)90356-5.
Withdrawal from chronic ethanol intake results in a syndrome of tremor and hyperexcitability, which can progress to seizures and death. Drugs used therapeutically to alleviate the syndrome have sedative actions and dependence liability of their own. The basis of the syndrome is unclear, although ethanol affects many neuronal functions, including membrane calcium conductance. Calcium channel blocking drugs have been used in cardiovascular disorders; they bind to high affinity sites in the brain but have few overt actions on the central nervous system. We have tested the effects of four calcium channel antagonists on the ethanol withdrawal syndrome in rats. Nitrendipine and nimodipine abolished all spontaneous seizures and prevented or reduced seizures following an audiogenic stimulus, and mortality. Verapamil significantly decreased seizure incidence and both it and flunarizine lowered mortality. The dihydropyridines were considerably more effective than diazepam in the withdrawal syndrome but had little effect on pentylenetetrazol seizures, against which diazepam gave good protection. The calcium channel inhibitors showed no sedative activity in normal animals. The results provide evidence that alterations in calcium conductance may be involved in the ethanol withdrawal syndrome and offer possibilities for the development of non-sedative therapeutic treatment of this syndrome.
长期摄入乙醇后戒断会导致震颤和过度兴奋综合征，该综合征可能会发展为癫痫发作甚至死亡。用于治疗该综合征的药物本身具有镇静作用和成瘾性。尽管乙醇会影响许多神经元功能，包括膜钙电导，但该综合征的发病机制尚不清楚。钙通道阻滞剂已用于治疗心血管疾病；它们能与大脑中的高亲和力位点结合，但对中枢神经系统几乎没有明显作用。我们测试了四种钙通道拮抗剂对大鼠乙醇戒断综合征的影响。尼群地平和尼莫地平消除了所有自发性癫痫发作，并预防或减少了听源性刺激后的癫痫发作及死亡率。维拉帕米显著降低了癫痫发作的发生率，它和氟桂利嗪都降低了死亡率。在戒断综合征方面，二氢吡啶类药物比地西泮有效得多，但对戊四氮诱发的癫痫发作几乎没有作用，而地西泮对戊四氮诱发的癫痫发作有很好的保护作用。钙通道抑制剂在正常动物中没有镇静活性。这些结果表明，钙电导的改变可能与乙醇戒断综合征有关，并为开发该综合征的非镇静性治疗方法提供了可能性。
