Abstract
The non-peptide NK1 receptor antagonist, CP-96,345, and its 2R,3R enantiomer CP-96,344, which is not an NK1 receptor antagonist (IC50 > 10 microM), were evaluated for antinociceptive and anti-inflammatory activities in several classical models of pain and inflammation in the rat. Both CP-96,345 and CP-96,344 reduced carrageenin-induced paw oedema and hyperalgesia, and attenuated the second phase of formalin-induced paw licking with equal potency. These results indicate that NK1 antagonism is not responsible for the activity of (+/-)-CP-96,345 in the above animal models.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Birch P. J., Harrison S. M., Hayes A. G., Rogers H., Tyers M. B. The non-peptide NK1 receptor antagonist, (+/-)-CP-96,345, produces antinociceptive and anti-oedema effects in the rat. Br J Pharmacol. 1992 Mar;105(3):508–510. doi: 10.1111/j.1476-5381.1992.tb09008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Constantine J. W., Lebel W. S., Woody H. A. Inhibition of tachykinin-induced hypotension in dogs by CP-96,345, a selective blocker of NK-1 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1991 Oct;344(4):471–477. doi: 10.1007/BF00172588. [DOI] [PubMed] [Google Scholar]
- Dubuisson D., Dennis S. G. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977 Dec;4(2):161–174. doi: 10.1016/0304-3959(77)90130-0. [DOI] [PubMed] [Google Scholar]
- Lecci A., Giuliani S., Patacchini R., Viti G., Maggi C. A. 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. Neurosci Lett. 1991 Aug 19;129(2):299–302. doi: 10.1016/0304-3940(91)90485-c. [DOI] [PubMed] [Google Scholar]
- Lembeck F., Donnerer J., Tsuchiya M., Nagahisa A. The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol. 1992 Mar;105(3):527–530. doi: 10.1111/j.1476-5381.1992.tb09013.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowe J. A., 3rd, Drozda S. E., Snider R. M., Longo K. P., Zorn S. H., Morrone J., Jackson E. R., McLean S., Bryce D. K., Bordner J. The discovery of (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1- azabicyclo[2.2.2]-octan-3-amine as a novel, nonpeptide substance P antagonisst. J Med Chem. 1992 Jul 10;35(14):2591–2600. doi: 10.1021/jm00092a009. [DOI] [PubMed] [Google Scholar]
- Nagahisa A., Kanai Y., Suga O., Taniguchi K., Tsuchiya M., Lowe J. A., 3rd, Hess H. J. Antiinflammatory and analgesic activity of a non-peptide substance P receptor antagonist. Eur J Pharmacol. 1992 Jul 7;217(2-3):191–195. doi: 10.1016/0014-2999(92)90847-w. [DOI] [PubMed] [Google Scholar]
- Snider R. M., Constantine J. W., Lowe J. A., 3rd, Longo K. P., Lebel W. S., Woody H. A., Drozda S. E., Desai M. C., Vinick F. J., Spencer R. W. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science. 1991 Jan 25;251(4992):435–437. doi: 10.1126/science.1703323. [DOI] [PubMed] [Google Scholar]