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Vol. 285, Issue 3, 1113-1122, June 1998
Department of Pharmacology and Toxicology, College of Medicine,
University of Arkansas for Medical Sciences, Little Rock, Arkansas
The development of treatment strategies for drug intoxication has been
hindered in part by the lack of clinically useful antagonists. Consequently, the major goal of these studies was to determine whether
a monoclonal antibody Fab fragment (of IgG) could be used as an
effective drug class-selective antagonist and to understand better the
dose-response relationships for reversing CNS drug toxicity. Changes in
drug-induced locomotor effects in a rat model were used to assess the
ability of the antiphencyclidine (anti-PCP) Fab to reverse the
behavioral effects of PCP and other potent arylcyclohexylamines. In
experiments to determine the pharmacodynamics of Fabinduced
antagonism of behavioral effects, the Fab completely reversed all
PCP-induced locomotor effects in a Fab dose-dependent manner with a
minimal effective dose of 0.18 mole-equivalents of Fab and an
ED50 value of about one-third mole-equivalent. 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 further tested by
treatment of the behavioral effects induced by the structurally
unrelated locomotor stimulant (+)methamphetamine. The antibody did not
effectively reverse the effects of methamphetamine-induced locomotor
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.
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