The pharmacodynamics of dilevalol

Dilevalol, the R-R1 isomer of labetalol, has been shown in animal studies to be a non-selective beta-adrenoceptor antagonist with beta 2-agonist activity and minimal alpha-antagonist activity. This paper describes the results of studies in man which have investigated the dose dependency and selectivity of dilevalol as an adrenoceptor antagonist and demonstrated its lack of alpha-antagonist activity. It also describes the results of studies which have investigated the magnitude of its partial agonist activity and demonstrated the selectivity of the partial agonist activity for the beta 2-adrenoceptor. Oral dilevalol 200 mg reduces an exercise tachycardia by about 25% and 400 mg does not increase the effect. Dilevalol 200 mg had no effect on the rise in blood pressure induced by infusions of phenylephrine, demonstrating its lack of alpha-antagonist activity. The increases in heart rate, systolic blood pressure, forearm blood flow and finger tremor induced by infusions of salbutamol are inhibited by dilevalol 200 and 400 mg and propranolol 80 mg to a similar degree indicating the lack of selectivity of the beta-antagonist activity of dilevalol. The effects of increasing oral doses of dilevalol on sleeping heart rate were used to assess the magnitude of its partial agonist activity. Heart rate four hours after dilevalol 200 and 400 mg was seven beats per minute higher than after placebo. Dilevalol 200 and 400 mg did not alter daytime supine heart rate, blood pressure or cardiac output but did increase forearm blood flow and finger tremor indicating that the partial agonist activity is mainly at the beta 2-adrenoceptor.