Guanabenz Acetate (WY-8678) is an selective agonist ofα2a-adrenergic receptor,α2b-adrenergic receptorandα2c-adrenergic receptorwithpEC50of 8.25, 7.01 and ~5, respectively. In vitro
Guanabenz at a concentration of 30 μM causes a time-dependent loss of nNOS-activity, which is present in cytosol prepared from rat nNOS transfected HEK 293 cells, with a Ki of 1 μM. Guanabenz can induce a concentration-dependent loss of nNOS activity. Within the first 3 h of treatment, 50 μM Guanabenz decreases the accumulation of nitrite and nitrate by approximately 75% in cells. Treatment of HEK 293 cells for 24 h with Guanabenz (100 μM) causes an approximately 35% decrease in the amount of immunodetectable nNOS protein. Guanabenz enhances proteolysis of the protein with the half-life decreasing by one-half from 20 to 10 h. Guanabenz is active against [ PSI+] prion in the yeast-based assay independent of its agonist activity on α2-adrenergic receptors. Guanabenz (10 μM) promote complete PrPSc clearance in mammalian MovS6 cell-based assay.
In vivo
Guanabenz injected i.v. in doses of 0.1 mg/kg causes an initial increase in blood pressure followed by a prolonged fall and a decrease in cardiac output, contractile force and heart rate in anesthetized dogs, which requires the presence of sympathetic tone. Guanabenz inhibits pressor responses to various procedures which initiate general sympathetic discharge. Guanabenz also antagonizes responses to sympathetic nerve stimulation. Guanabenz injected at doses of 0.5 mg/kg and above lowers blood pressure and heart rate in unanesthetized hypertensive rats and dogs. Cell Data
