Wessinger W D, Balster R L
Pharmacol Biochem Behav. 1987 Jun;27(2):323-32. doi: 10.1016/0091-3057(87)90576-4.
The effects of phencyclidine (PCP) alone and in combination with the CNS depressants, pentobarbital (PB) or ethanol (ETOH), were determined in mice using the inverted screen test and in rats using disruption of milk drinking behavior. The effects of PB and ETOH alone, and in combination, were also determined so that the PCP combinations could be compared to this clinically relevant interaction. These homergic drug interactions were analyzed using the dose-addition model by isobolographic analyses. Most drug combinations resulted in shifts to the left of the dose-effect curves relative to the dose-effect curves for the drugs alone; in no cases were shifts to the right (antagonism) observed. In general, the interactions between PCP and ETOH or PB were quantitatively less (infra-additive) than the interaction between the CNS depressants (dose-additive) when studied in mice. In the rat studies, the interactions between PCP and ETOH or PB were, overall, quantitatively greater (dose-additive or supra-additive) than the ETOH-PB interactions (infra-additive). Since even infra-additive interactions may result in substantially enhanced effects, these results suggest that coabuse of PCP with CNS depressant drugs could produce marked behavioral toxicity.
在小鼠中采用倒屏试验、在大鼠中采用扰乱舔乳行为的方法，测定了苯环己哌啶（PCP）单独使用以及与中枢神经系统抑制剂戊巴比妥（PB）或乙醇（ETOH）联合使用的效果。还测定了PB和ETOH单独使用以及联合使用的效果，以便将PCP联合用药的情况与这种临床相关的相互作用进行比较。通过等效应线分析，使用剂量相加模型对这些同类药物相互作用进行了分析。与单独使用药物的剂量效应曲线相比，大多数药物组合导致剂量效应曲线左移；未观察到右移（拮抗）的情况。总体而言，在小鼠中研究时，PCP与ETOH或PB之间的相互作用在数量上比中枢神经系统抑制剂之间的相互作用（剂量相加）要小（低于相加）。在大鼠研究中，PCP与ETOH或PB之间的相互作用总体上在数量上比ETOH - PB相互作用（低于相加）更大（剂量相加或超相加）。由于即使是低于相加的相互作用也可能导致效应大幅增强，这些结果表明PCP与中枢神经系统抑制药物共同滥用可能产生显著的行为毒性。
