Presynaptic Effect of Clonidine Antagonized by the Tetramine Disulphide, Benextramine

Abstract

1 The presynaptic a-adrenoceptor blocking activity of the newly synthesized a-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 a-adrenoceptors. 3 Clonidine reduced the effect of high-voltage stimulation, presumably by stimulating presynaptic a-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 a-adrenoceptors against benextramine blockade.

Y2‐receptor‐mediated selective inhibition of slow, inhibitory postsynaptic potential in submucous neurones of guinea‐pig caecum

“…There are, however, no NPY-preferring receptor antagonists, with suitable receptor-subtype selectivity, available at present. The tetramine disulphide, benextramine, has been proposed as an irreversible NPY-preferring receptor antagonist (Doughty et al, 1990) but this drug is also an irreversible antagonist at a-adrenoceptors (Belleau et al, 1982) probably including the subtype (M2-) mediating the slow i.p.s.p. (North & Surprenant, 1985).…”