Non-specific actions of the non-peptide 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 pIC50 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 pIC50 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.
Department of Pharmacology, University of Lund, Sweden.
Z Y
ZY
Wang
S R
SR
Tung
G R
GR
Strichartz
R
R
Håkanson
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007498:Iris / Q000187:drug effects; D054833:Isoindoles; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011343:Procaine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011892:Rana catesbeiana; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012584:Sciatic Nerve / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D000779:Anesthetics, Local; D001549:Benzamides; D001713:Biphenyl Compounds; D007211:Indoles; D054833:Isoindoles; D010880:Piperidines; D018039:Receptors, Tachykinin; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D011343:Procaine; C073839:SR 48968; C005298:benoxinate; C066892:CP 96345; D002045:Bupivacaine