Antagonism of Acetylcholine by Adrenaline Antagonists

Abstract

Phenoxybenzamine antagonized the inhibitory action of acetylcholine on the guineapig isolated atrium. The antagonism was slow in onset, very slowly reversible, and could be overcome by increased concentrations of acetylcholine. In contrast, atropine inhibited the action of acetylcholine quickly, and the effect disappeared soon after withdrawal. The pAio of phenoxybenzamine (2 hr of contact) was 6.8, and that of atropine (30 min of contact) was 8.4. In the presence of atropine phenoxybenzamine did not exert a slowly reversible antagonism, and the dose-ratio of acetylcholine returned to normal soon after withdrawal of both drugs. Phenoxybenzamine also antagonized acetylcholine in the guinea-pig isolated ileum, but with higher concentrations acetylcholine did not overcome the antagonism. The pAio (60 min of contact) was 6.6. The pAio of chlorpromazine in the atrium (2 hr of contact) and ileum (60 min of contact) was 5.9. Phentolamine, 2-diethylaminomethylbenzo-1,4-dioxan hydrochloride (883 F), and yohimbine antagonized acetylcholine in the atrium and ileum but required higher concentrations than chlorpromazine.

Presynaptic Effect of Clonidine Antagonized by the Tetramine Disulphide, Benextramine

“…A similar phenomenon was described by Benfey & Grillo (1963). In the guinea-pig isolated atrium the phenoxybenzamine blockade of the negative chronotropic effect of acetylcholine was slow in onset and offset and the atropine blockade had a fast onset and offset.…”

Antisympathomimetic and Antifibrillatory Effects of Pronethalol and Propranolol

“…While a concentration of 0.016 ,ug/ml. (0.071 ,uM) of acetylcholine reduced the amplitude of contraction 50% (Benfey & Grillo, 1963), 50% of the maximal increase of the amplitude of contraction was observed in the seventeen atria used in this study with 0.18±0.03 pg/ml. (mean and standard error) of noradrenaline (0.53 PAM).…”

“…Propranolol does not exhibit a particularly high degree of potency, judged from the fact that on the guinea-pig isolated atrium the a-receptor blocking drug, phenoxybenzamine, had apA10 with acetylcholine of 6.8 and atropine had apA10 of 8.4 (Benfey & Grillo, 1963). Thus the a-receptor blocking drug was a more potent antagonist of acetylcholine than was the P-receptor blocking drug of noradrenaline.…”

Cardiac adrenoceptors at low temperature and the adrenoceptor interconversion hypothesis

“…Thus 0.1 jIM phenoxybenzamine inhibited the chronotropic and inotropic effects of acetylcholine on guinea-pig atrium (Benfey & Grillo, 1963); 0.78 gM phenoxybenzamine caused a 50% inhibition of neuronal noradrenaline uptake and 2.8 gM phenoxybenzamine caused a 50% inhibition of extraneuronal noradrenaline uptake in rat heart (Iversen, 1973); 10 jiM dibenamine inhibited the chronotropic effect of isoprenaline (Krell & Patil, 1969), and 29 gM phenoxybenzamine inhibited the chronotropic effect of noradrenaline on guinea-pig atrium (Adler-Graschinsky, Langer & Rubio, 1972).…”