Tolerance to the cataleptic effect of the N-methyl-D-aspartate (NMDA) receptor antagonists in pigeons: cross-tolerance between PCP-like compounds and competitive NMDA antagonists.
Journal of Pharmacology and Experimental Therapeutics November 1, 1992 Y. Lu, C. France, J. Woods
Pigeons given daily injections of either phencyclidine (PCP) or CGS 19755, two types of NMDA receptor antagonists, developed tolerance to the drugs' cataleptic effects. PCP tolerance initially shifted the dose-effect curve 5-fold to the right, and with a higher chronic dose produced a complete downward shift. CGS 19755 tolerance shifted its curve 10-fold to the right. Cross-tolerance occurred between PCP and other PCP-like compounds as well as to CGS 19755, and from CGS 19755 to another competitive NMDA antagonist and to PCP-like compounds. Sensitivity to etomidate or pentobarbital remained unchanged, showing selectivity. The symmetric cross-tolerance suggests both drug classes produce catalepsy through a similar mechanism of inhibiting neurotransmission at NMDA excitatory synapses.