Atipamezole(MPV1248) is an alpha-adrenoceptor antagonist with high affinity and selectivity for the alpha 2-receptor.
in vitro: The alpha2-adrenoceptor antagonist atipamezole was a potent inhibitor of aldosterone release (range 10-1000 nM) . In receptor binding studies [( 3H]-clonidine and [3H]-prazosin displacement) an alpha 2/alpha 1 selectivity ratio of 8526 was obtained for atipamezole, while idazoxan and yohimbine showed ratios of 27 and 40, respectively. Atipamezole had also about a 100 times higher affinity on alpha 2-adrenoceptors than the reference compounds .
in vivo: In vivo studies of [3H]atipamezole demonstrated good penetration into the brain (0.3-1.8% injected dose/g at 5 min, depending upon brain region). In addition, [3H]atipamezole displayed rapid in vivo clearance of nonspecific binding such that at 1 h following an i.v. injection of the drug (100 microCi/animal, rat tail vein administration) the pattern of radioactivity in the brain correlated very well with the receptor distribution as seen by in vitro autoradiography . In mice, medetomidine-induced sedation was effectively antagonized by atipamezole .
. Jager LP, et al. Effects of atipamezole, detomidine and medetomidine on release of steroid hormones by porcine adrenocortical cells in vitro. Eur J Pharmacol. 1998 Apr 3;346(1):71-6.
. Biegon A, et al. Quantitative in vitro and ex vivo autoradiography of the alpha 2-adrenoceptor antagonist [3H]atipamezole. Eur J Pharmacol. 1992 Nov 24;224(1):27-38.
. Virtanen R, et al. Highly selective and specific antagonism of central and peripheral alpha 2-adrenoceptors by atipamezole. Arch Int Pharmacodyn Ther. 1989 Jan-Feb;297:190-204.