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. 1991 Dec;104(4):823–828. doi: 10.1111/j.1476-5381.1991.tb12513.x

The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers.

E Riva 1, T Mennini 1, R Latini 1
PMCID: PMC1908821  PMID: 1687367

Abstract

1. We compared the alpha 1-, alpha 2- and beta 1-adrenoceptor blocking potencies of labetalol with those of its two stereoisomers (RR and SR) in pithed rats and in homogenized rat cerebral cortex and heart. 2. In pithed rats, labetalol and the RR-SR combination were given orally either at doses of 25 and 50 mg kg-1 body wt. or intravenously at doses of 1 and 5 mg kg-1 body wt. Prazosin 4 and 20 micrograms kg-1 body wt. and propranolol 1 and 5 mg kg-1 body wt., were given intravenously for comparison studies of potency at alpha 1- and beta 1-adrenoceptors, respectively. Effects were studied before and after i.v. administration of either phenylephrine (at doses which increased the mean arterial pressure by approximately 80 mmHg) or isoprenaline (at doses that increased heart rate by approximately 100 beats min-1). 3. In pithed rats, labetalol and the RR-SR combination antagonized, in a dose-dependent manner, the pressor effect of phenylephrine (P less than 0.05) and the chronotropic effect of isoprenaline (P less than 0.05). Following both oral and intravenous dosing, the RR-SR combination was twice potent as labetalol in terms of alpha 1- and beta 1-adrenoceptor antagonism at equivalent doses. 4. Labetalol and the enantiomers lacked affinity at alpha 2-adrenoceptors while at alpha 1-adrenoceptors the order of potency was prazosin much greater than RR-SR greater than labetalol. At beta 1-adrenoceptors, the affinity of the compound RR-SR was about 3 times that of labetalol.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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