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d ‐Sotalol reduces heart rate in vivo through a β‐adrenergic receptor–independent mechanism
Author(s) -
Yasuda Sally Usdin,
Barbey Jean T,
FunckBrentano Christian,
Wellstein Anton,
Woosley Raymond L
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.48
Subject(s) - sotalol , atenolol , antagonist , pharmacology , heart rate , medicine , receptor , chemistry , endocrinology , blood pressure , atrial fibrillation
d ‐Sotalol was developed as an antiarrhythmic agent with a relative lack of antagonist activity at β‐adrenergic receptors. Exercise heart rate reduction has been observed after administration to humans. The purpose of this study was to determine directly whether this effect of d ‐sotalol was attributable to β ‐blockade. Plasma samples from normal volunteers who randomly received either atenolol, d ‐sotalol, or placebo were used in an in vitro radioreceptor assay to determine occupancy of β‐adrenergic receptors by antagonist present in the plasma. Occupancy was compared with the observed pharmacologie effects. A reduction in exercise heart rate of 7.7% ± 3.8% for d ‐sotalol and 15.9% ± 3.0% for atenolol occurred with β 1 ‐adrenergic receptor occupancy of 0% and 33.9% ± 21.4%, respectively. Absence of antagonist effect in the radioreceptor assay eliminates the potential role of β 1 ‐blockade in d ‐sotalol— induced heart rate reduction. This effect is most likely a result of prolongation of the sinus node action potential duration. Clinical Pharmacology and Therapeutics (1993) 53, 436–442; doi: 10.1038/clpt.1993.48