Effect of labetalol and YM-09538 on neuronal uptake of (3H)norepinephrine in the rat vas deferens.
Labetalol and YM-09538 are combined alpha and beta receptor antagonists with demonstrated antihypertensive activity. Both compounds inhibited the uptake of (3H)norepinephrine into nerves in the rat vas deferens. However, labetalol was approximately 5 fold more potent than YM-09538 as an inhibitor of neuronal uptake. Inhibition of neuronal uptake occurred at concentrations 43 and 3800 times higher than necessary for inhibition of alpha receptors by labetalol and YM-09538, respectively. Thus YM-09538 shows a greater separation between neuronal uptake blocking properties and alpha receptor blocking properties than labetalol. This separation of activities may contribute to greater antihypertensive efficacy of YM-09538 relative to labetalol.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004983:Ethanolamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000294:innervation / Q000378:metabolism; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007741:Labetalol; D009638:Norepinephrine; C032473:amosulalol; D000096926:Benzenesulfonamides