title: Comparison of the effects of (+/-) CP 96,345 and L-668,169 on neurokinin receptor mediated responses in rat and guinea-pig isolated tissues.
abstract: The effects of (+/-) CP 96,345 and L-668,169 on NK1-, NK2- and NK3-receptor mediated contractile responses were compared in guinea-pig and rat isolated smooth muscle tissues. Both (+/-) CP 96,345 and L-668,169 inhibited NK1-mediated responses in guinea-pig ileum (pA2 = 9.3 and 6.4 respectively) but not in rat bladder (pKB = < 6 and < 5.5 respectively) consistent with species differences in NK1-receptor pharmacology. Both compounds showed some selectivity in inhibiting NK1-receptor evoked responses in guinea-pig ileum compared to their inhibitory effects on NK2-receptor mediated responses in guinea-pig bladder and rat ileum and NK3-mediated responses in guinea-pig ileum and rat portal vein.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex.
authors.forename: Z
authors.initials: Z
authors.lastname: Razzaque
authors.forename: J
authors.initials: J
authors.lastname: Longmore
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004600:Eledoisin / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D009928:Organ Specificity; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011169:Portal Vein / Q000187:drug effects; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D013045:Species Specificity; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C054724:senktide; C062618:substance P, Sar(9)-Met(O2)(11)-; C076509:L 668169; D013373:Substance P; D004600:Eledoisin; C066892:CP 96345