caa a22 4500 469078227 CHVBK 20180323132941.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00173546 doi (NATIONALLICENCE)springer-10.1007/BF00173546 CP-96,345, a non-peptide antagonist of substance P: II. Actions on substance P-induced hypotension and bronchoconstriction, and on depressor reflexes in mammals [Elektronische Daten] [T. Griesbacher, J. Donnerer, F. Legat, F. Lembeck] Summary: In order to extend the in vivo pharmacological profile of CP-96,345 ((2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride), a non-peptide antagonist of substance P, the compound was tested against substance P-induced effects on blood pressure in rabbits and on respiration pressure in guinea-pigs. In addition, CP-96,345, and its inactive (2R, 3R)-enantiomer, CP-96,344, were also tested in 2 models involving presumably substance P-mediated reflexes in the rat. The fall in blood pressure evoked by i.v. injections of substance P in the rabbit was inhibited by 0.3 µmolkg−1, CP-96,345 iv. for at least 30 min, and almost abolished, for at least 2 h, by 3 µmol kg−1. In guinea-pigs, the bronchoconstriction induced by i.v. injections of substance P, but not that in response to histamine or bradykinin, was inhibited by CP-96,345 (0.6 and 6.0 µmolkg−1, i.v.) in a dose-dependent manner and this inhibition lasted for 40 min and 70 min, respectively. CP-96,345 (3-20 µmolkg−1, i.v.) reduced depressor reflexes in response to stimulation of peripheral capsaicin-sensitive neurones in the rat. However, the inhibition was not dose-dependent and was also seen with the inactive enantiomer, CP-96,344. This effect can hardly be attributed to receptor-specific effects of CP-96,345 and may be related to unspecific actions such as those involved in the cardiac depression exhibited by both enantiomers. The present results show that CP-96,345 is a potent antagonist of substance P in vivo. The failure of CP-96,345 to show a specific inhibition of the depressor reflexes which are thought to be mediated by substance P released within the spinal cord requires further investigation. Springer-Verlag, 1992 Substance P nationallicence Tachykinin antagonist nationallicence CP-96,345 nationallicence Blood pressure nationallicence Bronchoconstriction nationallicence Griesbacher T. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut Donnerer J. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut Legat F. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut Lembeck F. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 323-327 0028-1298 346:3<323 1992 346 210 https://doi.org/10.1007/BF00173546 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00173546 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Griesbacher T. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut NATIONALLICENCE 700 1- Donnerer J. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut NATIONALLICENCE 700 1- Legat F. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut NATIONALLICENCE 700 1- Lembeck F. Institut für Experimentelle and Klinische Pharmakologie, Karl-Franzens-Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 323-327 0028-1298 346:3<323 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer