Clonidine-d4 is intended for use as an internal standard for the quantification of clonidine by GC- or LC-MS. Clonidine is an agonist of α2-adrenergic receptors (α2-ARs; Kis = 61.66, 69.18, and 134.9 nM for α2A-, α2B-, and α2C-ARs, respectively).1 It stimulates [35S]GTPγS binding to HEK293 cell membranes expressing the human receptors with EC50 values of 26.92, 56.23, and 912.01 nM for α2A-, α2B-, and α2C-ARs, respectively. Clonidine also binds to I1-imidazoline sites in a variety of cell and tissue types (Kds = 4-15 nM).2 It induces relaxation of isolated mesenteric artery rings precontracted with norepinephrine when used at a concentration of 10 μM.3 Clonidine (10 μM) also induces membrane hyperpolarization and reduces norepinephrine-induced depolarization in isolated mesenteric artery rings. Clonidine (0.1 and 1 μg/kg) reduces mean blood pressure and heart rate when administered via microinjection to the nucleus reticularis lateralis (NRL) of anesthetized normotensive cats.4 Formulations containing clonidine have been used in the treatment of hypertension.
1.Jasper, J.R., Lesnick, J.D., Chang, L.K., et al.Ligand efficacy and potency at recombinant α2 adrenergic receptors: Agonist-mediated [35S]GTPγS bindingBiochem. Pharmacol.55(7)1035-1043(1998) 2.Ernsberger, P., Graves, M.E., Graff, L.M., et al.I1-imidazoline receptors. Definition, characterization, distribution, and transmembrane signalingAnn. N.Y. Acad. Sci. 763(1)22-42(1995) 3.Silva, E.G., Feres, T., Vianna, L.M., et al.Dual effect of clonidine on mesenteric artery adrenoceptors: Agonistic (alpha-2) and antagonistic (alpha-1)J. Pharmacol. Exp. Ther.277(2)872-876(1996) 4.Bousquet, P., Feldman, J., and Schwartz, J.Central cardiovascular effects of alpha adrenergic drugs: Differences between catecholamines and imidazolinesJ. Pharmacol. Exp. Ther.2301(1)232-236(1984)