Js. Hardin et al., PHARMACODYNAMICS OF A MONOCLONAL ANTIPHENCYCLIDINE FAB WITH BROAD SELECTIVITY FOR PHENCYCLIDINE-LIKE DRUGS, The Journal of pharmacology and experimental therapeutics, 285(3), 1998, pp. 1113-1122
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.