Effects of anti-phencyclidine and anti-(+)-methamphetamine monoclonal antibodies alone and in combination on the discrimination of phencyclidine and (+)-methamphetamine by pigeons

Abstract

Rationale

Drug-specific monoclonal antibodies against phencyclidine (PCP) and (+)-methamphetamine [(+)-METH] should bind to these drugs to block their discriminative stimulus effects.

Objectives

To determine if mouse monoclonal antibodies against PCP and (+)-METH can block the discriminative stimulus effects of the drugs in pigeons.

Materials and methods

Pigeons were trained to discriminate among intramuscular injections of saline, 1 mg/kg PCP, and 2 mg/kg (+)-METH. After responding stabilized, cumulative dose–response curves were obtained for PCP and (+)-METH. Doses of an anti-PCP antibody at 620 mg/kg (anti-PCP mAb6B5) with a K _D of 1.3 nM for PCP and no measurable affinity for (+)-METH and 1,000 mg/kg doses of anti-(+)-METH antibody (anti-METH mAb6H7) with a K _D of 41 nM for (+)-METH and no measurable affinity for PCP were subsequently administered, first alone and later in combination after which the dose–response curves were redetermined.

Results

When the antibodies were given alone, the anti-PCP antibody blocked the discriminative stimulus effects of PCP, but not those of (+)-METH, and the anti-(+)-METH antibody blocked the discriminative stimulus effects of (+)-METH, but not those of PCP. The anti-PCP antibody shifted the PCP dose–response curve further to the right and for a longer time than the anti-(+)-METH antibody shifted the dose response curve for (+)-METH. When the anti-PCP and anti-(+)-METH antibodies were administered on the same day, the discriminative stimulus effects of both drugs were completely blocked 1 day after antibody administration.

Conclusions

These experiments demonstrate the high specificity of the antibodies for the drugs to which they bind and show that monoclonal antibodies can be combined to antagonize the effects of more than one drug.