NONSPECIFIC ACTIONS OF THE NONPEPTIDE TACHYKININ RECEPTOR ANTAGONISTS, CP-96,345, RP-67580 AND SR-48968, ON NEUROTRANSMISSION

1 Three non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, were found to inhibit the electrically-evoked, tachykinin-mediated contractile responses of the rabbit iris sphincter in a concentration-dependent fashion; the pIC(50) values were 5.6 +/- 0.01, 5.4 +/- 0.07 and 4.8 +/- 0.03, respectively. 2 These antagonists also inhibited the electrically-evoked, parasympathetic response of the rabbit iris sphincter and the sympathetic response of the guinea-pig vas deferens in a concentration-dependent manner; the pIC(50) values were 0.3-1.2 log units lower than those recorded for the tachykinin-mediated responses. 3 Two local anaesthetics, bupivacaine and oxybuprocaine, were also found to inhibit the tachykinin-mediated, cholinergic and sympathetic contractile responses in these tissues in a concentration-dependent manner; the concentration ranges for producing the inhibition were similar to those of the non-peptide tachykinin receptor antagonists. 4 On the sciatic nerves of frogs, the tachykinin receptor antagonists inhibited action potentials in a concentration-dependent manner; the potency of the three drugs was similar to that of bupivacaine. 5 Our results suggest that, in addition to blocking tachykinin receptors, the non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, may exert non-specific inhibitory effects on neurotransmission.