The effects of chronic treatment with the dihydropyridine, Bay K 8644, were studied on the ethanol withdrawal syndrome, in vivo and in vitro. 2. Addition of racemic Bay K 8644 to the drinking mixture, throughout the chronic ethanol treatment, decreased the behavioural excitability seen during ethanol withdrawal in vivo. 3. All the signs of hyperexcitability in field potentials in the isolated hippocampal slice, caused by ethanol withdrawal, were decreased by the chronic administration of Bay K 8644. 4. These effects resembled those previously reported for chronic administration of calcium channel antagonists; racemic Bay K 8644 has both calcium channel activating and antagonist properties. 5. Measurement of brain levels of Bay K 8644 at the end of the chronic treatment showed that the compound reached micromolar concentrations during the treatment, but none could be detected in the tissues at the time of the above measurements. 6. It is possible that the results might be explained by predominance of the calcium channel antagonist properties of this compound, owing to the high central concentrations achieved during the treatment. Tolerance to the calcium channel activating properties of Bay K 8644 may also have occurred during the chronic treatment.
摘要
研究了二氢吡啶类药物Bay K 8644长期治疗对乙醇戒断综合征的体内和体外影响。2. 在整个慢性乙醇治疗过程中，将消旋Bay K 8644添加到饮水中，可降低体内乙醇戒断期间出现的行为兴奋性。3. 慢性给予Bay K 8644可降低乙醇戒断引起的离体海马切片场电位中的所有兴奋迹象。4. 这些作用类似于先前报道的钙通道拮抗剂长期给药的作用；消旋Bay K 8644具有钙通道激活和拮抗特性。5. 在慢性治疗结束时测量Bay K 8644的脑内水平表明，该化合物在治疗期间达到微摩尔浓度，但在上述测量时在组织中未检测到。6. 由于治疗期间达到的高中枢浓度，该化合物的钙通道拮抗特性占优势可能解释了这些结果。在慢性治疗期间也可能发生了对Bay K 8644钙通道激活特性的耐受性。
