Competitive inhibition of acetylcholinesterase by bretylium: possible mechanism for its induction of norepinephrine release.
The antiarrhythmic drug bretylium tosylate competitively inhibits acetylcholinesterase activity. The Ki values for the inhibition of the purified enzyme (from electric eel), and acetylcholinesterase activity of crude rat ventricular and cortical homogenates were 6 X 10(-5), 3 X 10(-5), and 8 X 10(-5) M respectively. These values are close to the concentrations of the drug known to induce norepinephrine release from cardiac adrenergic presynaptic vesicles. It is suggested that inhibition of acetylcholinesterase activity by bretylium induces norepinephrine release through the effect of accumulated acetylcholine on nicotinic receptors in adrenergic nerve terminals.
Schreiber
G
G
Sokolovsky
M
M
D000110:Acetylcholinesterase / Q000378:metabolism*; D000122:Acetylthiocholine / Q000494:pharmacology; D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology*; D001950:Bretylium Tosylate / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004593:Electrophorus; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009411:Nerve Endings / Q000201:enzymology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats
D001949:Bretylium Compounds; D002800:Cholinesterase Inhibitors; D000122:Acetylthiocholine; D001950:Bretylium Tosylate; D000110:Acetylcholinesterase; D009638:Norepinephrine