Enantioselective inhibition of the formalin paw late phase by the NK1 receptor 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-dependent and complete inhibition of the late, but not the early, phase nociceptive response (paw licking). The ID50 for l-733,060 (0.17 mg/kg) revealed a greater than 50-fold separation in potency over its less active enantiomer l-733,061 (ID50 ≥ 10 mg/kg). In contrast, the non-brain penetrant quaternary ketone NK1 receptor antagonist, l-743,310 (3 mg/kg), did not attenuate the response to formalin, indicating that the antinociceptive effect of blockade of NK1 receptors by l-733,060 in this assay is centrally-mediated. These findings add to the preclinical evidence that NK1 receptor antagonists may be of therapeutic use as centrally-acting analgesics.