ENANTIOSELECTIVE INHIBITION OF THE FORMALIN PAW LATE-PHASE BY THE NK1RECEPTOR ANTAGONIST L-733,060 IN GERBILS

Intravenous administration of the NK1 receptor antagonist L-733,060 to gerbils 3 h before intraplantar injection of formalin caused a dose-d ependent and complete inhibition of the late, but not the early, phase nociceptive response (paw licking). The ID50 for L-733,060 (0.17 mg/k g) revealed a greater than 50-fold separation in potency over its less active enantiomer L-733,061 (ID50 greater than or equal to 10 mg/kg). In contrast, the non-brain penetrant quaternary ketone NK1 receptor a ntagonist, L-743,310 (3 mg/kg), did not attenuate the response to form alin, indicating that the antinociceptive effect of blockade of NK1 re ceptors by L-733,060 in this assay is centrally-mediated. These findin gs add to the preclinical evidence that NK1 receptor antagonists may b e of therapeutic use as centrally-acting analgesics.