Selective 2-adrenergic properties of dexmedetomidine over clonidine in the human forearm

Masuki, Shizue, Frank A. Dinenno, Michael J. Joyner, and John H. Eisenach. Selective 2-adrenergic properties of dexmedetomidine over clonidine in the human forearm. J Appl Physiol 99: 587–592, 2005. First published March 31, 2005; doi:10.1152/japplphysiol.00147.2005.— We tested the hypothesis that dexmedetomidine (Dex) has greater 2vs. 1 selectivity than clonidine and causes more 2-selective vasoconstriction in the human forearm. After local -adrenergic blockade with propranolol, forearm blood flow (plethysmography) responses to brachial artery administration of Dex, clonidine, and phenylephrine ( 1-agonist) were determined in healthy young adults before and after 2-blockade with yohimbine (n 10) or 1-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 phenylephrinemediated 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 2-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.