Antiphencyclidine monoclonal Fab fragments reverse phencyclidine-induced behavioral effects and ataxia in rats.
Antiphencyclidine monoclonal antibody binding fragments (anti-PCP Fab) were studied in rats as a possible treatment for phencyclidine (PCP) overdose. Each male Sprague-Dawley rat (n = 4 per group) received an i.v. dose of 1 mg/kg of PCP followed 5 min later (as toxicity maximized) by one of three treatments in a random cross-over design. The treatments were 1 ml of saline, a nonspecific polyclonal human Fab, or a high affinity (Kd = 1.8 nM) anti-PCP monoclonal Fab. The doses of the nonspecific and anti-PCP Fab were 0.3, 1.0 and 3.0 times the mole equivalent (mol-eq) dose of PCP. Changes in locomotor activity and ataxia were the best indicators of PCP-induced behaviors among several time-dependent behavioral changes that were evaluated. PCP administration followed by saline treatment resulted in increases in locomotor activity and ataxia that declined to base line after 35 to 40 min. Anti-PCP Fab at 1.0 and 3.0 times the mol-eq dose of PCP significantly (P < .05) and rapidly reversed PCP-induced behaviors to base-line values. Although the 0.3 mol-eq dose of Fab appeared to slightly decrease the behavioral toxicity, the effects were not statistically different from controls in most cases. No significant effects on PCP-induced behaviors were observed after any dose of the nonspecific Fab. In addition, pharmacological and immunological specificity were tested further by treatment of MK-801 {(+)-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine-}-induced behavioral effects. MK-801 is a PCP-like, noncompetitive N-methyl-D-aspartate receptor antagonist which is structurally unrelated to PCP. The anti-PCP Fab treatment had no effect on MK-801-induced locomotor activity. These data clearly show that anti-PCP Fab is a specific PCP antagonist that can rapidly reverse PCP-induced behavioral toxicity in the rat.
Valentine
J L
JL
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
Mayersohn
M
M
Wessinger
W D
WD
Arnold
L W
LW
Owens
S M
SM
D000818:Animals; D001259:Ataxia / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010622:Phencyclidine