Jl. Valentine et al., ANTIPHENCYCLIDINE MONOCLONAL FAB FRAGMENTS REVERSE PHENCYCLIDINE-INDUCED BEHAVIORAL-EFFECTS AND ATAXIA IN RATS, The Journal of pharmacology and experimental therapeutics, 278(2), 1996, pp. 709-716
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 treatm
ents were 1 mi of saline, a nonspecific polyclonal human Fab, or a hig
h affinity (K-d = 1.8 nM) anti-PCP monoclonal Fab. The doses of the no
nspecific and anti-PCP Fab were 0.3, 1.0 and 3.0 times the mole equiva
lent (mol-eq) dose of PCP. Changes in locomotor activity and ataxia we
re the best indicators of FOR-induced behaviors among several time-dep
endent behavioral changes that were evaluated. PCP administration foll
owed by saline treatment resulted in increases in locomotor activity a
nd ataxia that declined to base line after 35 to 40 min. Anti-FOR 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 behaviora
l toxicity, the effects were not statistically different from controls
in most cases, No significant effects on PCP-induced behaviors were o
bserved after any dose of the nonspecific Fab. In addition, pharmacolo
gical and immunological specificity were tested further by treatment o
f MK-801 +)-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten -5,10-imin
e-}-induced behavioral effects. MK-801 is a PCP-like, noncompetitive N
-methyl-D-aspartate receptor antagonist which is structurally unrelate
d to PCP. The anti-PCP Fab treatment had no effect on MK-801-induced l
ocomotor activity. These data clearly show that anti-PCP Fab is a spec
ific PCP antagonist that can rapidly reverse POP-induced behavioral to
xicity in the rat.