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 .
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D004983:Ethanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017981:Receptors, Neurotransmitter; D010656:Phenylephrine; D015016:Yohimbine; C024892:medroxalol; D011433:Propranolol; D003000:Clonidine; D009638:Norepinephrine