title: (+/-)-CP-96,345, a selective tachykinin NK1 receptor antagonist, has non-specific actions on neurotransmission.
abstract: 1. The non-specific effects of the non-peptide tachykinin receptor antagonist (+/-)-CP-96,345, were assessed in several smooth muscle-nerve preparations. The preparations were the iris sphincter muscle of the rabbit and the taenia coli, vas deferens and seminal vesicle of the guinea-pig. 2. (+/-)-CP-96,345 concentration-dependently inhibited the electrically evoked, tachykinin-mediated contractile responses of the iris sphincter and the taenia coli. The pIC50 values were 5.4 +/- 0.2 (mean +/- s.e.mean) and 5.7 +/- 0.08 respectively. 3. (+/-)-CP-96,345 also inhibited non-tachykinin-mediated contractile responses to electrical stimulation of the iris sphincter, taenia coli, vas deferens and seminal vesicle. The pIC50 values were 4.3 +/- 0.02, 4.8 +/- 0.03, 4.7 +/- 0.02 and 4.4 +/- 0.05 respectively. These values differ significantly from the pIC50 values of the inhibition of the tachykinin-mediated response in the iris sphincter and taenia coli. 4. (+/-)-CP-96,345 was without effect on carbachol- and noradrenaline-evoked contractions of the iris sphincter but inhibited carbachol- and prostaglandin F2 alpha (PGF2 alpha)-evoked contractions of the taenia coli. 5. We suggest that (+/-)-CP-96,345, apart from its NK1 receptor blocking activity, induces non-specific suppression of neurotransmission, exerted at both pre- and post-junctional sites.
authors.affiliation: Department of Pharmacology, University of Lund, Sweden.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D018039:Receptors, Tachykinin; D009435:Synaptic Transmission / Q000187:drug effects*; D015320:Tachykinins / Q000037:antagonists & inhibitors; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D002217:Carbachol; D015237:Dinoprost; C066892:CP 96345; D009638:Norepinephrine