Toxicity of phencyclidine and ethanol in combination.

Alcohol and drug research Pub Date : 1985-01-01
B L Brunet, R J Reiffenstein, T Williams, L Wong
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Abstract

The role of ethanol in phencyclidine-related death and loss of motor co-ordination was studied in male ICR albino mice. LD50s, and ED50s for loss of righting reflex, and for the "rotarod" test were determined for each drug in the presence of various doses of the other. Isobolograms (plots of equieffective dose combinations) of these LD50s and ED50s showed that low doses of ethanol reduced the LD50 of phencyclidine (PCP) by about 20%, while higher doses (1-3 g/kg) of ethanol were without further effect. In contrast to effects on lethality, there was synergism (potentiation) of loss of motor co-ordination. Doses of ethanol above 1 g/kg reduced the ED50 of PCP for loss of righting from about 60 mg/kg to 1-3 mg/kg. Similarly, low doses of PCP (less than 40 mg/kg) reduced the ED50 of ethanol from 3 g/kg to 1 g/kg. There was a slight but consistent synergism between the drugs in the rotarod test over the range of effective doses (0.25-2.0mg/kg PCP and 0.1-1.2 g/kg ethanol). It is concluded that consumption of ethanol does not greatly increase the risk of death from PCP overdose; however the severe adverse effects on motor co-ordination of moderate doses of PCP together with moderate doses of ethanol are greatly potentiated by doses of the other drug. It is estimated that commonly used doses could result in total loss of motor ability, which could explain the prevalence of accidental deaths (especially drowning) when PCP and ethanol have been consumed together.

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苯环利定与乙醇联用的毒性。
在雄性ICR白化小鼠中研究了乙醇在苯环利定相关死亡和运动协调丧失中的作用。在不同剂量的另一种药物存在的情况下,测定每一种药物的ld50,以及扭转反射丧失的ed50和“旋转棒”试验的ed50。这些LD50s和ED50s的等效图(等效剂量组合图)显示,低剂量乙醇使苯环利定(PCP)的LD50降低了约20%,而高剂量(1-3 g/kg)乙醇没有进一步的影响。与对致死率的影响相反,运动协调性丧失有协同作用(增强)。超过1 g/kg的乙醇剂量使PCP的ED50从约60 mg/kg降低到1-3 mg/kg。同样,低剂量的PCP(低于40 mg/kg)将乙醇的ED50从3 g/kg降低到1 g/kg。在有效剂量范围内(0.25-2.0mg/kg PCP和0.1-1.2 g/kg乙醇),rotarod试验中药物之间存在轻微但一致的协同作用。由此得出结论:乙醇的摄入不会大大增加PCP过量致死的风险;然而,中等剂量的PCP和中等剂量的乙醇对运动协调的严重不良影响会因另一种药物的剂量而大大增强。据估计,通常使用的剂量可能导致运动能力的完全丧失,这可以解释当PCP和乙醇一起食用时意外死亡(特别是溺水)的流行。
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