Role of NK1 tachykinin receptors in thermonociception: Effect of (±)-CP 96,345, a non-peptide substance P antagonist, on the hot plate test in mice

The interaction of the NK1 receptor antagonist CP‐96,345 with L‐type calcium channels and its functional consequences

“…This observation was confirmed by us using the racemic mixture ( ± )-CP-96,345, and extended to other tissues in a preliminary study (Boyle et al, 1991). Similarly 'unspecific' effects with ( ± )-CP-96,345 in several in vitro smooth muscles have been reported (Lecci et al, 1991;Wang & Hakanson, 1991;Legat et al, 1992). Furthermore, both 344 have been reported to be equally effective in producing a marked transient hypotensive response when administered in vivo to anaesthetized dogs , rats , and rabbits .…”

“…Thus the recent report that ( ± )-CP-96,345 blocked the hyperalgesia and cedema caused by intraplantar injection of carrageenin in the rat, and was active in blocking the nociceptive response in the formalin test (Birch et al, 1992), cannot now be taken as evidence that activation of the NK, receptor occurred in these tests, with the subsequent report that these actions were obtained with both of the separate enantiomers CP-96,345 and CP-96,344 (Nagahisha et al, 1992). Similarly the conclusion that substance P acting via the NK1 receptor mediates thermal nociception, based on the observation that ( ± )-CP-96,345 is antinociceptive after intrathecal administration in the mouse hot-plate test (Lecci et al, 1991), must be reconsidered. Particularly pertinent to such uses of this compound, in tests for antinociceptive activity after local administration, is the recent report that ( ± )-CP-96,345 blocks voltage-dependent sodium currents, and is 50 times more active than lignocaine in this respect (Caesar et al, 1993).…”

“…The recent discovery of CP-96,345, a selective non-peptide antagonist with high affinity for the NK, receptor (Snider et al, 1991), thus represents a major advance towards this end. However, while CP-96,345 has been reported in functional and binding studies to possess high selectivity for the NK, receptor (Beresford et al, 1991;Lecci et al, 1991;Rouissi et al, 1991;Snider et al, 1991), on I Author for correspondence.…”

Facilitatory effects of selective agonists for tachykinin receptors on cholinergic neurotransmission: evidence for species differences

“…) was synthesized as previously described (Lecci et al, 1991). The amino acid sequence of the peptide agonist and antagonists used in this study is shown in Table 1.…”

Neurogenic “Off” Contractions Are Mediated by NK2-Receptors in the Circular Muscle of Guinea Pig Ileum

“…However, an assumption for substantial, if not total, blockade of NK,-receptors with 10-' M CP-96,345 may be evidenced by the fact that 10-7 M CP-96,345 almost completely inhibited 10-' M substance P-induced contrac tions in the presence of atropine in the longitudinal mus cle of the guinea pig ileum (N. Suzuki et al, unpublished results). Furthermore, in light of the pA2 of 8.1 to 8.9 reported for CP-96,345 in blocking NK,-receptors in the longitudinal muscle of guinea pig ileum (10)(11)(12), it may be presumed that NK,-receptors were blocked to a large extent with 10-'M CP-96,345 in the circular muscle of guinea pig ileum. Then the fact that FK224, but not CP 96,345, blocked the "off" contractions in the presence of atropine may suggest that the "off" contraction is mediat ed mainly by NK2-receptors in the circular muscle of guinea pig ileum.…”