The interaction of
phencyclidine,
dexoxadrol, their analogs and stereoisomers with
phencyclidine receptors was compared to their ability to induce stereotyped behavior and
ataxia after i.c.v. administration to rats. The order of potency for binding to
phencyclidine receptors revealed that among the stereoisomers of
phencyclidine derivatives, the (+) isomer was more potent than the (-) isomer. A similar order of potency of
phencyclidine derivatives and degree of stereoselectivity was seen in the assays for stereotyped behavior and
phencyclidine receptor interactions, which resulted in a good correlation between the relative potencies for binding to
phencyclidine receptors and inducing stereotyped behavior. However, the order of potency for induction of
ataxia and the stereoselectivity was different than that seen in the assays for
phencyclidine receptor interactions and stereotyped behavior. A comparison of relative potencies for binding to
phencyclidine receptors to induction of
ataxia still resulted in a good fit to a straight line, but the line did not intersect the origin, indicating that a non-
phencyclidine receptor component is also involved in mediating
ataxia.
Dextrorphan and 2-methyl-3,3-diphenyl-3-propylamine were equipotent as
phencyclidine in
phencyclidine receptor and behavioral assays. The order of potency for interacting with
phencyclidine receptors and inducing
phencyclidine-like behavior by the isomers of
cyclazocine were opposite to that of other
phencyclidine analogs. Also, the order of potency for induction of
ataxia by the isomers of
N-allylnormetazocine was opposite to that for
phencyclidine receptor interactions.
Ethylketocyclazocine did not induce any stereotyped behavior or
ataxia, indicating that it is unlikely that a
kappa opioid receptor interaction plays a role in mediating
ataxia. Furthermore, stereotyped behavior and
ataxia were not due to interactions with mu, kappa or
delta opioid receptors as
naloxone did not antagonize the behavioral effects of
phencyclidine, (-)
cyclazocine or (-)
N-allylnormetazocine. These results indicate that stereotyped behavior is mediated by
phencyclidine receptors, whereas
ataxia is mediated by more than just
phencyclidine receptors.