Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of ambenonium, a reversible cholinesterase inhibitor, in rats was investigated following intravenous administration of the drug. Mean residence time and steady state volume of distribution were 23-36 min and 0.20-0.311 kg-1, respectively, and were dose independent at the dose of 0.3-3 mumole kg-1. Total body clearance of 8.2 ml min-1 kg-1 over 0.3 mumole kg-1 was slightly increased to 11.3 ml min-1 kg-1 at 3 mumole kg-1. Renal clearance was also increased with the increase of the dose, while hepatobiliary clearance was substantially constant. Ambenonium was highly concentrated in the liver, kidney, spleen, and lung. About 30 per cent of the dose is concentrically stored in the liver at 6 h after administration, and had not disappeared after 24 h.
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PMID:Pharmacokinetics of ambenonium, a reversible cholinesterase inhibitor, in rats. 180 66

Ambenonium is known to be an inhibitor of acetylcholinesterase, and recent data have shown this drug to antagonize muscarinic receptors as well. This latter property was confirmed by Schild analyses of ambenonium-induced blockade of responses to bethanechol in guinea-pig ileal longitudinal smooth muscle, taenia caeci, trachea and rat anococcygeus muscle. Statistical analysis showed ambenonium to be a simple competitive antagonist of responses to bethanechol in these tissues with pKB values in each tissue not significantly different from each other (mean pKB = 6.0). However, considerable variability in pKB estimates was encountered when ambenonium was utilized to block responses to acetylcholine. Ambenonium was a less potent antagonist of tissue responses to acetylcholine, and the underestimation in the pKB (as compared to that obtained with bethanechol) could be eliminated by prior treatment of tissues with the acetylcholinesterase inhibitor neostigmine. These data suggested that ambenonium had a dual effect on tissue responses to acetylcholine-producing potentiation by blockade of acetylcholinesterase and concomitant antagonism by blockade of muscarinic receptors. The Schild regressions obtained for ambenonium antagonism of acetylcholine responses formally satisfied criteria for simple competitive antagonism of a homogenous population of receptors (linear regression, slope equal to unity). The fact that these regressions yielded erroneous apparent pKB values suggests how two properties of a drug in one molecule could provide misleading information about drug receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Self-cancellation of drug properties as a mode of organ selectivity: the antimuscarinic effects of ambenonium. 285 86

The inhibition of human motor endplate cholinesterase by anticholinesterase compounds was studied using isolated muscle membrane preparation. Ambenonium was most potent, and edrophonium was least potent in inhibiting motor endplate cholinesterase. The slope of the regression line for inhibition of motor endplate cholinesterase was greatest for ambenonium, and smallest for neostigmine and edrophonium. These compounds were less potent inhibitors of plasma cholinesterase. Ambenonium was more specific, and other compounds were less specific inhibitors of motor endplate cholinesterase. In myasthenic patients, these compounds produced adequate inhibition of motor endplate cholinesterase even in the presence of relatively mild plasma cholinesterase inhibition.
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PMID:Inhibition of human motor endplate cholinesterase by anticholinesterase compounds. 711 48