The irreversible alpha-blocker benextramine interacts with two different thiol groups.
beta-Haloalkylamines bind at two sites on the adrenergic alpha-receptor, one related to the noradrenaline-recognition site and the other possibly concerned with the calcium channel. In order to verify whether this might apply to other alpha-blockers the tetramine disulfide benextramine was selected owing to its unprecedented covalent selectivity towards the adrenergic alpha-receptor. The fast acting beta-haloalkylamine DMPEA and the "classical" calcium antagonist verapamil were used for protection experiments against benextramine blockade of rat vas deferens adrenergic alpha-receptor. It was demonstrated that two target thiols are probably involved in benextramine binding and one of them might possibly be located at the periphery of, or masked within, the calcium channel which may be connected physiologically to the adrenergic alpha-receptor. However, the hypothesis that the present results could indicate the selective interaction of benextramine with two different subtypes of the adrenergic alpha-receptor is also discussed.
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D003538:Cystamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D013438:Sulfhydryl Compounds; C029998:benextramine; D003538:Cystamine; D002118:Calcium; D009638:Norepinephrine