Disease relevance of Guanoxabenz

• Compared with yohimbine, these analogues were, respectively, 36 and 18 times more potent intravenously and 5 and 7.5 times more potent orally in their antagonism of guanoxabenz-induced mydriasis in the pentobarbitone-anaesthetized rat [1].

High impact information on Guanoxabenz

• Moreover, when the spleen membranes were extensively washed for 30 min with buffers at 25 degrees, the guanoxabenz high-affinity binding disappeared [2].
• The mechanism for formation of high affinity binding of guanoxabenz (1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine) to alpha2-adrenoceptors by the rat spleen cytosol was studied [3].
• The formation of guanoxabenz high-affinity binding was also inhibited in a time- and concentration-dependent fashion by preincubating the membranes with the LW03 N-hydroxyguanidine analogue of guanoxabenz [2].
• Neither corynanthine nor prazosin reversed the guanoxabenz-induced mydriasis [4].
• The action of the enzyme on guanoxabenz resulted in the formation of guanabenz [1-(2,6-dichlorobenzylidene-amino)-3-guanidine]; the product formation could be monitored by HPLC and its identity was confirmed by NMR analysis [5].

Anatomical context of Guanoxabenz

• Similarly, antagonist potency in the vas deferens was highly correlated with antagonist activity in reversing the centrally-mediated mydriasis induced by the selective alpha 2-adrenoceptor agonist, guanoxabenz, in pentobarbitone-anaesthetized rats [6].
• However, by contrast to the results with the spleen, the guanoxabenz competition curves for the spinal cord and cerebral cortex were monophasic and resolved only into one site fits, the Kd of guanoxabenz being about 4000 nmol/l for both tissues [7].
• We conclude that 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 [8].
• Moreover, when the rat RNG alpha 2B-adrenoceptor was expressed in COS-7 cells and its binding properties tested using [3H]-MK 912 binding, guanoxabenz, LT 11 as well as a number of other drugs inhibited the ligand binding at a single alpha 2-adrenoceptor site; the drug Kds being practically the same as those found for the neonatal rat lung [9].

Associations of Guanoxabenz with other chemical compounds

• These results suggest that the guanabenz N-hydroxylation is mediated via CYP1A2, whereas the corresponding guanoxabenz N-reduction is catalyzed by an enzyme system composed of cytochrome b5, NADH cytochrome b5-reductase, and benzamidoxime reductase [10].

Gene context of Guanoxabenz

• Formation of guanoxabenz from guanabenz in human liver. A new metabolic marker for CYP1A2 [10].
• However, the competition curves for guanoxabenz were definitely biphasic and resolved into two site fits, indicating that guanoxabenz was binding to both high affinity (Kd = 35 nmol/l) and low affinity (Kd = 8900 nmol/l) alpha 2A-adrenoceptor sites in the proportions 57% and 43%, respectively [7].

Analytical, diagnostic and therapeutic context of Guanoxabenz

• The alpha 2-adrenoceptor antagonists yohimbine and mianserin were also effective in blocking guanoxabenz-induced EEG synchronisation but had a lower potency than did RX 781094 [11].

References