Smooth muscle relaxant effects of tetrazepam on isolated guinea-pig and rat trachealis

1 Tetrazepam (TZP) suppressed rat and guinea-pig tracheal tone by 100% and there was no difference in the relaxant effects against tone induced by 120 mM K+, carbachol (0.5 mu M) or histamine (100 mu M). 2 In trachealis pretreated with propranolol (1 mu M), the relaxant response to TZP was unaltered. 3 TZP (10 mu M) added to the relaxant effect of isoprenaline in tissues precontracted with carbachd. 4 The relaxant effect of TZP appears to be unrelated to peripheral benzodiazepine receptors (PBRs) because pretreatment with PK 11195 (1 mu M) did not modify its effect. 5 Diltiazem (a calcium antagonist) was capable of relaxing the KCl (120 mM) or carbachol (0.5 mu M) precontracted trachea, although at a different dose range than that of TZP. 6 The tracheal relaxation by TZP may be due to competition at some point in the chain of events linking carbachol, K+ or histamine to contraction, interacting with one of the transduction pathways, probably Ca2+. This inhibition of contraction is not related to the high affinity PBRS.