Cott J M, Ogren S O
J Neural Transm. 1980;48(4):223-40. doi: 10.1007/BF01250658.
The interactions between ethanol and antidepressant drugs (both tricyclics and newer non-tricyclics) were studied in mice. The ability of these drugs to enhance the sedative effects of ethanol at two different doses (3.2 and 4.0 g/kg) was measured. The percentage of mice losing the righting-reflex was used for the lower dose, and the duration of ethanol-induced sleep was used at the higher dose. The relative order of potency was amitriptyline greater than or equal to imipramine > maprotiline = mianserin > desipramine greater than or equal to chlorimipramine > iprindole greater than or equal to alaproclate > norzimelidine greater than or equal to zimelidine. Amitriptyline (60 mg/kg) caused death in all mice when combined with 4.0 g/kg ethanol. Clinically established antidepressants which enhanced ethanol sedation only at doses considerably above therapeutic levels were zimelidine and iprindole. The relative potency of the antidepressants to enhance ethanol sedation is correlated with their inherent sedative properties which are in turn related to their ability to block central 5-HT, alpha-NA, muscarinic and H1-receptors. Amitriptyline (20 mg/kg) was found to increase ethanol plasma levels to 202, 167 and 132% of control values at 30, 60 and 90 min after ethanol administration, respectively. Desipramine, mianserin and alaproclate also increased ethanol plasma levels initially, but to a lesser extent. These findings suggest that in addition to their sedative effect, several antidepressants, particularly amitriptyline, are likely to interact with ethanol by increasing its concentration in plasma.
在小鼠中研究了乙醇与抗抑郁药物（三环类和新型非三环类）之间的相互作用。测定了这些药物在两种不同剂量（3.2和4.0 g/kg）下增强乙醇镇静作用的能力。较低剂量时使用失去翻正反射的小鼠百分比，较高剂量时使用乙醇诱导睡眠的持续时间。效力的相对顺序为：阿米替林大于或等于丙咪嗪>马普替林 = 米安色林>地昔帕明大于或等于氯米帕明>茚满二酮大于或等于阿普氯胺>去甲替林大于或等于齐美利定。当与4.0 g/kg乙醇联合使用时，阿米替林（60 mg/kg）导致所有小鼠死亡。临床上已确定仅在剂量远高于治疗水平时才增强乙醇镇静作用的抗抑郁药物是齐美利定和茚满二酮。抗抑郁药物增强乙醇镇静作用的相对效力与其固有的镇静特性相关，而固有的镇静特性又与它们阻断中枢5-羟色胺、α-去甲肾上腺素、毒蕈碱和H1受体的能力有关。发现阿米替林（20 mg/kg）在乙醇给药后30、60和90分钟分别将乙醇血浆水平提高到对照值的202%、167%和132%。地昔帕明、米安色林和阿普氯胺最初也会提高乙醇血浆水平，但程度较小。这些发现表明，除了镇静作用外，几种抗抑郁药物，特别是阿米替林，可能通过增加乙醇在血浆中的浓度而与乙醇相互作用。
