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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Selectivity of acebutolol, atenolol, and metoprolol in healthy volunteers estimated by the extent the drugs occupy beta 2-receptors in the circulating plasma.

The selectivity of acebutolol, atenolol, and metoprolol in healthy volunteers was estimated by determining the extent to which the drugs occupied beta 1-receptors of rabbit lung and beta 2-receptors of rat reticulocytes in the circulating plasma after drug intake. This ex vivo method had the advantage of including all drug components contributing to the drug-receptor equilibrium in vivo and of excluding the factors regulating organ sensitivity to catecholamine stimulation. The oral doses of 400 mg acebutolol, 100 mg atenolol, and 100 mg metoprolol were administered to six healthy male volunteers using a double-blind, randomized, and cross-over study design. The three drugs occupied beta 1-receptors to a similar extent at 2 hours after drug intake. The receptor fraction occupied by metoprolol at 3 to 8 hours after drug intake was usually smaller, however (analysis of variance for repeated measures, P < .05) than that of the other drugs. Acebutolol occupied significantly larger fractions of beta 2-receptors (analysis of variance for repeated measures, P < .05) than did atenolol and metoprolol. Therefore, at an identical beta 1-receptor occupancy, the beta 2-receptor occupancy of acebutolol was larger than that of the other agents. Apparently, active metabolites decreased markedly the selectivity of acebutolol, but not that of metoprolol. The receptor occupancy of the agents was well in agreement with the literature concerning the selectivity, intensity, and time-course of drug actions after identical doses.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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