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.