Physicochemical and pharmacological studies of some 8-substituted decahydroisoquinolines

Several compounds of a diastereoisomeric series of 8-substituted 2-methyldecahydroisoquinolines have been found to be equipotent or more potent than quinidine in prolonging the refractory period of isolated guinea pig atria. The effects of selected compounds on the intracellularly recorded transmemb...

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Veröffentlicht in:Journal of medicinal chemistry 1976-03, Vol.19 (3), p.385-391
Hauptverfasser: Mathison, Ian W., Morgan, Phillip H., Wojciechowski, Norbert J., Bandura, Jack P., Wennemark, James R.
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container_end_page 391
container_issue 3
container_start_page 385
container_title Journal of medicinal chemistry
container_volume 19
creator Mathison, Ian W.
Morgan, Phillip H.
Wojciechowski, Norbert J.
Bandura, Jack P.
Wennemark, James R.
description Several compounds of a diastereoisomeric series of 8-substituted 2-methyldecahydroisoquinolines have been found to be equipotent or more potent than quinidine in prolonging the refractory period of isolated guinea pig atria. The effects of selected compounds on the intracellularly recorded transmembrane action potential of isolated canine Purkinje fibers indicated a mechanism of action similar to quinidine in causing a large decrease in the rising velocity of rapid depolarization. Acid dissociation constants and percentage buccal membrane absorption have been determined, in an attempt to correlate these physiochemical properties and the stereochemistry of the derivatives with the observed antiarrhythmic potency. Compounds with high lipophilicity and the trans ring-juncture stereochemistry generally appear to possess superior potency.
doi_str_mv 10.1021/jm00225a009
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source ACS Publications; MEDLINE
subjects Absorption
Action Potentials - drug effects
Animals
Cell Membrane - metabolism
Chemical Phenomena
Chemistry, Physical
Dogs
Electric Stimulation
Guinea Pigs
Heart Atria - drug effects
Heart Rate - drug effects
Humans
In Vitro Techniques
Isoquinolines - metabolism
Isoquinolines - pharmacology
Kinetics
Membrane Potentials - drug effects
Purkinje Fibers - drug effects
Purkinje Fibers - physiology
Refractory Period, Electrophysiological - drug effects
Stereoisomerism
Structure-Activity Relationship
title Physicochemical and pharmacological studies of some 8-substituted decahydroisoquinolines
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