THE NEUROKININ-1 RECEPTOR ANTAGONIST, SENDIDE, EXHIBITS ANTINOCICEPTIVE ACTIVITY IN THE FORMALIN TEST

Sendide is a selective and extremely potent antagonist of neurokinin-1 (NK1) receptors in the mouse spinal cord. The antinociceptive activit ies of sendide, an antagonist of NK1 receptors, and its analogue, [D-T rp(7)]sendide have been examined after intrathecal (i.t.) administrati ons in the mouse paw formalin test. Intrathecal administration of send ide (in pmol) reduced both the early and late phases of the formalin-i nduced licking response. [D-Trp(7)]sendide also produced a significant antinociceptive response with less potent activity than sendide. Even highest doses (4000 pmol sendide and 8000 pmol [D-Trp(7)]sendide) exa mined, there was no motor paralysis of the hindlimbs. Intrathecal morp hine inhibited both the early and late phases of the formalin-induced licking response in a dose-dependent manner. The results indicate that the antinociceptive effects of sendide and [D-Trp(7)]sendide may be m ediated at NK1 receptors in the formalin-induced nociception.