Noradrenergic response to acute ethanol administration in healthy subjects: comparison with intravenous yohimbine.
Noradrenergic response to acute ethanol administration in healthy subjects: comparison with intravenous yohimbine.
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健康受试者对急性乙醇给药的去甲肾上腺素能反应：与静脉注射育亨宾的比较。
DOI：
10.1007/bf02245830
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发表时间：
1995
影响因子：
3.4
通讯作者：
Charney,DS
中科院分区：
文献类型：
--
作者：
McDougle,CJ;Krystal,JH;Price,LH;Heninger,GR;Charney,DS
采用双盲、安慰剂对照设计，比较了口服乙醇[1.1 ml/kg 95%乙醇作为20%（体积）溶液给药]和静脉注射α 2肾上腺素能受体拮抗剂盐酸育亨宾（0.4 mg/kg）单独和联合给药的作用。12名健康受试者完成了4个试验日，在此期间评估了药物对中毒和焦虑的主观测量、去甲肾上腺素（NE）代谢物3-甲氧基-4-羟基苯基乙二醇（MHPG）和皮质醇的血浆水平以及心血管指数的影响。与安慰剂相比，急性口服乙醇显著增加了中毒和焦虑的主观测量值、血浆MHPG和坐位收缩压。与安慰剂相比，静脉注射育亨宾显著增加中毒和焦虑的主观测量值、血浆MHPG和皮质醇以及血压。乙醇诱导的血浆MHPG的增加显著大于育亨宾，而育亨宾导致焦虑，血浆皮质醇和血压测量的显着增加比乙醇。与单独使用乙醇或育亨宾相比，联合使用乙醇和育亨宾具有明显的增加急性中毒严重程度的累加效应，并导致血浆MHPG反应显著高于单独使用任何一种药物。尽管必须考虑乙醇给药对NE代谢的药代动力学影响，但这些结果表明，在健康受试者中，急性乙醇给药的致醉和致焦虑作用可能与NE周转率增加（通过血浆MHPG测定）相关。此外，这些结果表明，乙醇和育亨宾可以起到相加作用，以增加乙醇中毒，他们可以通过不同的生理机制增加NE营业额。
The effects of oral administration of ethanol [1.1 ml/kg 95% ethanol administered as a 20% (by volume) solution] and intravenous administration of the alpha2adrenergic receptor antagonist yohimbine hydrochloride (0.4 mg/kg), alone and in combination, were compared using a double-blind, placebo-controlled design. Twelve healthy subjects completed 4 test days during which drug effects on subjective measures of intoxication and anxiety, plasma levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and cortisol, and cardiovascular indices were assessed. Acutely administered oral ethanol significantly increased the subjective measures of intoxication and anxiety, plasma MHPG, and sitting systolic blood pressure compared with placebo. Intravenous yohimbine significantly increased subjective measures of intoxication and anxiety, plasma MHPG and cortisol, and blood pressure relative to placebo. The ethanol-induced increase in plasma MHPG was significantly greater than that following yohimbine, whereas yohimbine resulted in significantly greater increases in anxiety, plasma cortisol, and blood pressure measurements than ethanol. The combined administration of ethanol and yohimbine had a clear additive effect of increasing the severity of acute intoxication compared with ethanol or yohimbine alone, and resulted in a significantly greater plasma MHPG response compared with either drug given alone. Although the pharmacokinetic effects of ethanol administration on NE metabolism must be considered, these findings suggest that the intoxicating and anxiogenic effects of acute ethanol administration may be associated with increased NE turnover, as measured by plasma MHPG, in healthy human subjects. In addition, these results indicate that ethanol and yohimbine may act additively to increase ethanol intoxication and that they may increase NE turnover through different physiological mechanisms.