PHARMACODYNAMICS OF A MONOCLONAL ANTIPHENCYCLIDINE FAB WITH BROAD SELECTIVITY FOR PHENCYCLIDINE-LIKE DRUGS

The development of treatment strategies for drug intoxication has been hindered in part by the lack of clinically useful antagonists. Conseq uently, the major goal of these studies was to determine whether a mon oclonal antibody Fab fragment (of IgG) could be used as an effective d rug class-selective antagonist and to understand better the dose-respo nse relationships for reversing CNS drug toxicity. Changes in drug-ind uced locomotor effects in a rat model were used to assess the ability of the antiphencyclidine (anti-PCP) Fab to reverse the behavioral effe cts of PCP and other potent arylcyclohexylamines. In experiments to de termine the pharmacodynamics of Fab-induced antagonism of behavioral e ffects, the Fab completely reversed all PCP-induced locomotor effects in a Fab dose-dependent manner with a minimal effective dose of 0.18 m ole-equivalents of Fab and an ED50 value of about one-third mole-equiv alent. The anti-PCP Fab also completely reversed the locomotor effects induced by two other structurally related potent analogs of PCP: 1-[1 -(2-thienyl)cyclohexyl]piperidine and N-ethyl-1-phenylcyclohexylamine. In addition, pharmacological and immunological selectivity was furthe r tested by treatment of the behavioral effects induced by the structu rally unrelated locomotor stimulant (+)methamphetamine. The antibody d id not effectively reverse the effects of methamphetamine-induced loco motor activity. These results indicate that antibody-based medications can be developed to treat toxicity caused by classes of drugs as well as by individual drugs.