Non-specific effects of the tachykinin NK1 receptor antagonist, CP-99,994, in antinociceptive tests in rat, mouse and gerbil

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Abstract

We have examined the antinociceptive activity of the potent and selective tachykinin NK1 receptor antagonist, CP-99,994, and its less active enantiomer, CP-100,263, in a variety of models in rat, mouse and gerbil. Administered systemically to gerbil or mouse CP-99,994 but not CP-100,263 stereo selectively inhibited a caudally directed biting and scratching elicited by intrathecal administration of the tachykinin NK1 receptor agonist, GR73632. In contrast, both CP-99,994 (ED50 = 3 (1−6) μmol · kg−1 s.c.) and CP-100,263 (4 (2–10)), were equipotent at inhibiting acetylcholine-inuced abdominal constrictions in mice. Similarly, both enantiomers were also equipotent in reducing formalin-induced licking in gerbil (CP-99,994 (10.1 (5.7–18.6)), CP-100,263 (13.8 (7.8.–27.1)) and rat (100 μmol · kg−1 s.c.). Finally, in the spinalised rat, CP-99,994 dose-dependently and significantly inhibited the flexion reflex evoked by noxious pinch (5.0 (3.3–7.5) μmol · kg−1 i.v.), whereas the less active enantiomer, CP-100,263, was without significant effect when tested up to 30 μmol · kg−1. Our results demonstrate that in the spinal cord, CP-99,994 exhibits a tachykinin NK1 receptor mediated antinociceptive action.

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