Guanabenz Acetate

Guanabenz Acetate is an selective agonist of α2a-adrenergic receptor, α2b-adrenergic receptor and α2c-adrenergic receptor with pEC50 of 8.25, 7.01 and ~5, respectively.

Sinoatrial and atrioventricular dysfunction associated with the use of guanabenz acetate.[Pubmed:3378199]

Can J Cardiol. 1988 Apr;4(3):146-8.

Guanabenz Acetate is an antihypertensive drug that is closely related to clonidine hydrochloride. Clonidine is well known to potentiate atrioventricular (AV) node conduction disturbances, but to date that effect has not been attributed to guanabenz. A case of electrocardiographic and electrophysiologic studies in a patient with both sinus and AV node conduction disturbances associated with the use of Guanabenz Acetate is reported. The sinus cycle length was increased by 50% after guanabenz and the sinus node recovery time was prolonged by 42%. AV block occurred proximal to the His bundle and His-ventricular prolongation of 42% also occurred. This drug should be used cautiously in patients with evidence of sinus or AV node dysfunction.

Effects of guanabenz acetate on the pacemaker activity of rabbit sinoatrial node cells.[Pubmed:2619423]

Arch Int Pharmacodyn Ther. 1989 Jul-Aug;300:209-17.

The effects of Guanabenz Acetate on the electrophysiological properties of isolated rabbit sinoatrial node were studied using conventional microelectrode and double-microelectrode voltage clamp methods and were compared with those of clonidine and guanethidine. In spontaneously beating sinoatrial node preparations, guanabenz decreased the heart rate, the maximum rate of rise (Vmax), the action potential amplitude and the rate of diastolic depolarization in a dose-dependent fashion, whereas the action potential duration at 50% repolarization was prolonged. In comparison with clonidine and guanethidine, the inhibitory potency of guanethidine on the heart rate is weaker than that of guanabenz and clonidine. On the current systems, the voltage clamp experiments showed that guanabenz reduced the slow inward current and the time-dependent potassium outward current. These observations indicate that guanabenz acts directly on cardiac tissues and its bradycardic action can be mainly explained by a reduction of delayed current systems.

Renal effects of infusion of rilmenidine and guanabenz in conscious dogs: contribution of peripheral and central nervous system alpha 2-adrenoceptors.[Pubmed:8564219]

Br J Pharmacol. 1995 Sep;116(1):1557-70.

1. We tested the renal effects of the alpha 2-adrenoceptor agonists, rilmenidine and guanabenz and the antagonists, 2-methoxyidazoxan and idazoxan, in conscious dogs. Our aim was to test the hypothesis that putative imidazoline (I) receptors influence renal function. We reasoned that since rilmenidine and guanabenz are selective for I1- and I2-binding sites respectively, an influence of one of these receptive sites on renal function would be reflected in qualitative differences between the effects of these agents. Moreover, effects mediated by putative I-receptors should be relatively resistant to antagonism by the selective alpha 2-adrenoceptor antagonist, 2-methoxyidazoxan. Since the effects of these drugs on renal function could be mediated in the central nervous system or periphery, the dogs were studied under both normal and ganglion-blocked conditions. 2. In dogs with intact autonomic reflexes, 2-methoxyidazoxan (15 micrograms kg-1 plus 0.6 micrograms kg-1 min-1) produced effects consistent with a generalized increase in sympathetic drive, including increases in mean arterial pressure and plasma renin activity, and a reduction in sodium excretion. In ganglion-blocked dogs, 2-methoxyidazoxan reduced sodium excretion but had no discernible effect on systemic or renal haemodynamics. We conclude that an alpha 2-adrenoceptor-mediated mechanism in the central nervous system tonically inhibits sympathetic drive in the conscious dog. 3. In ganglion-blocked dogs idazoxan (3-300 micrograms kg-1) dose-dependently increased arterial pressure. This was not abolished by concomitant administration of 2-methoxyidazoxan (0.3-30 micrograms kg-1). The pressor effect of idazoxan is therefore probably mediated by an agonist action at alpha 1-adrenoceptors. 4. The effects of infusions of rilmenidine (0.1-1.0 mg kg-1) and guanabenz (10-100 micrograms kg-1) were indistinguishable. They comprised dose-dependent increases in mean arterial pressure, urine excretion, and glomerular filtration rate (the latter in ganglion blocked dogs only), and dose-dependent reductions in heart rate, renal blood flow and sodium excretion (only in dogs with intact autonomic reflexes). All of these effects were antagonized by 2-methoxyidazoxan. 5. We conclude that the renal effects of rilmenidine and guanabenz infusions in conscious dogs are predominantly, if not completely, attributable to activation of alpha 2-adrenoceptors. Our results do not support the hypothesis that putative I-receptors contribute towards the renal effects of these agents.

Guanabenz. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension.[Pubmed:6352237]

Drugs. 1983 Sep;26(3):212-29.

Guanabenz is an orally active central alpha 2-adrenoceptor agonist. Its antihypertensive action is thought to result from a decrease in sympathetic outflow from the brain to the peripheral circulatory system as a result of stimulation of central alpha 2-adrenoceptors. In mild to moderate hypertension it is as effective as methyldopa and clonidine in lowering blood pressure when used as the sole treatment. As with these drugs, guanabenz may be combined with a diuretic to increase its blood pressure-lowering effect. The overall incidence of side effects seen with guanabenz was at least as high as with methyldopa or clonidine, and side effects such as drowsiness or dry mouth have been bothersome enough to lead to discontinuation of guanabenz therapy in some patients. However, particularly troublesome effects such as sodium retention, depression or sexual dysfunction which may occur with methyldopa or clonidine have not been reported with guanabenz.