Selective α2-adrenergic properties of dexmedetomidine over clonidine in the human forearm

Abstract

We tested the hypothesis that dexmedetomidine (Dex) has greater α2- vs. α1 selectivity than clonidine and causes more α2-selective vasoconstriction in the human forearm. After local β-adrenergic blockade with propranolol, forearm blood flow (plethysmography) responses to brachial artery administration of Dex, clonidine, and phenylephrine (α1-agonist) were determined in healthy young adults before and after α2-blockade with yohimbine ( n = 10) or α1-blockade with prazosin ( n = 9). Yohimbine had no effect on phenylephrine-mediated vasoconstriction but blunted Dex-mediated vasoconstriction (mean ± SE: −41 ± 5 vs. −11 ± 2%; before vs. after yohimbine) more than clonidine-mediated vasoconstriction (−39 ± 5 vs. −28 ± 4%; before vs. after yohimbine) ( P < 0.02). Prazosin blunted phenylephrine-mediated vasoconstriction (−39 ± 4 vs. −8 ± 2%; before vs. after prazosin) but had similar effects on both Dex- (−30 ± 4 vs. −39 ± 6%; before vs. after prazosin) and clonidine-mediated vasoconstriction (−29 ± 3 vs. −41 ± 7%; before vs. after prazosin) ( P > 0.7). Both Dex and clonidine reduced deep forearm venous norepinephrine concentrations to a similar extent (−59 ± 12 vs. −55 ± 10 pg/ml; Dex vs. clonidine, P > 0.6); this effect was abolished by yohimbine and blunted by prazosin. These results suggest that Dex causes more α2-selective vasoconstriction in the forearm than clonidine. The similar vasoconstrictor responses to both drugs after prazosin might be explained by the presynaptic effects on norepinephrine release.