Rupniak Nadia M J, Carlson Emma, Boyce Susan, Webb Janine K, Hill Raymond G
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow,Essex CM20 2QR, UK.
Pain. 1996 Sep;67(1):189-195. doi: 10.1016/0304-3959(96)03109-0.
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 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 > or = 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.
