Guanoxabenz (Hydroxyguanabenz) hydrochloride is an agonist of α2 adrenergic receptor. It has a Ki of 4000 nM and the fully activated form 40 nM for an α2A adrenoceptor[1][2][3].

The formation of high-affinity Guanoxabenz binding seems to be inhibited by a series of N-hydroxyguanidine analogs to Guanoxabenz, as well as by a series of metabolic inhibitors that included allopurinol, 1-chloro-2,4-dinitrobenzene, 5,59-dithiobis-(2-nitrobenzoic acid), cibacron blue, phenyl-p-benzoquinone, didox, and trimidox. The formation of Guanoxabenz high-affinity binding is also inhibited in a time- and concentration-dependent fashion by preincubating the membranes with the LW03 N-hydroxyguanidine analogue of Guanoxabenz [1]. The spleen cytosolic fraction mediates the reduction of Guanoxabenz to guanabenz, the latter having an almost 100-fold higher affinity for rat alpha2A-adrenoceptors than Guanoxabenz itself [2].

Guanoxabenz and guanabenz are both known as centrally active antihypertensive drugs. High affinity Guanoxabenz binding is induced in rat brain membranes after addition of NADH or NADPH cofactors. The rat cerebral cortex contains an enzymatic activity that may activate Guanoxabenz leading to formation of a metabolite showing high affinity for alpha 2-adrenoceptors [3]. Guanoxabenz (0.1-3 mg/kg, i.p.) causes a dose-related reduction in locomotor activity; a dose of 1 mg/kg is selected since this induces a pronounced and sustained behavioural hypoactivity [4]. Animal Model: Rats [4]. Dosage: 0.5 mg/kg (RX 781094 or saline vehicle was injected intravenously (tail vein) at the time of peak effect of the agonist (20min for clonidine and 30 min for Guanoxabenz). Administration: IP. Result: RX 781094 (0.1-1.0 mg/kg, i.v.) produces a rapid (< 5 set) and complete antagonism of the EEG and behavioural effects induced by clonidine and Guanoxabenz.