Presynaptic effect of clonidine antagonized by the tetramine disulphide, benextramine.
1 The presynaptic alpha-adrenoceptor blocking activity of the newly synthesized alpha-adrenoceptor blocking drug, benextramine, was evaluated in the isolated left atrium of the guinea-pig heart. 2 High-voltage stimulation increased the force of contraction of electrically driven atrial strips, presumably by releasing noradrenaline from sympathetic nerve endings. Like phentolamine, benextramine increased the effect of high-voltage stimulation, presumably by blocking presynaptic alpha-adrenoceptors. 3 Clonidine reduced the effect of high-voltage stimulation, presumably by stimulating presynaptic alpha-adrenoceptors. The inhibitory effect of clonidine was antagonized noncompetitively by benextramine and competitively by phentolamine. 4 Combined administration of benextramine and phentolamine only resulted in the competitive phentolamine antagonism. Thus phentolamine protected the presynaptic alpha-adrenoceptors against benextramine blockade.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors*; D003042:Cocaine / Q000494:pharmacology; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; C029998:benextramine; D001285:Atropine; D003042:Cocaine; D003000:Clonidine; D003538:Cystamine; D010646:Phentolamine