Analysis of the hypotensive effects of medroxalol and its enantiomers, MDL 17,330A and MDL 17,331A.

Medroxalol and two of its enantiomers (MDL 17, 330A , MDL 17, 331A ) were tested for activity at adrenergic receptors to clarify the mechanism(s) of the antihypertensive action of medroxalol . The potency order for blocking postsynaptic alpha 1-receptors in vivo in rats was similar to that reported in vitro. However, relatively high doses of these compounds were necessary to block alpha 1-receptors in vivo compared to their antihypertensive doses. Postsynaptic alpha 2-receptors were not blocked by medroxalol in vitro. Propranolol pretreatment of rats to block vascular beta 2-receptors antagonized much of the hypotensive response to medroxalol and its enantioners , most extensively with MDL 17, 330A , but much less with MDL 17, 331A . The potency rank order as beta 2-adrenergic agonists was the same as previously reported for these compounds as beta 1-adrenergic receptor antagonists. The stimulation of beta 2-adrenergic receptors in vascular smooth muscle appears to be an important factor in the hypotensive action of medroxalol .