Background:

Guanabenz is an orally active α2-adrenoceptor agonist with hypotensive effects [1]. The α2 adrenergic receptors belong to a family of G protein-coupled receptor (GPCR), mediate many physiological actions of the endogenous catecholamines adrenaline and noradrenaline. The α2-adrenoceptor agonists have been currently used as antihypertensives and as veterinary sedative anaesthetics. They have also been used experimentally in humans as adjuncts to anaesthesia, as spinal analgesics, and to treat opioid, nicotine and alcohol dependence and withdrawal [2].

In vitro: Maximum concentrations of guanabenz in plasma (1.2 to 5.2 ng/ml) reached 2 to 5 hours after administration of capsules containing 16 or 32 mg of 14C-labelled guanabenz. Guanabenz was 90% bound to human plasma proteins [1]. Guanabenz competed for imidazoline I2-binding sites in brown adipose tissue with Ki of 97 nM [3].

Clinical trials: Guanabenz has undergone trials in patients with mild to moderate hypertension. The dosage was in the range of 8 to 64 mg daily, the majority of patients being controlled on up to 32 mg/day. Guanabenz was an effective antihypertensive agent in about 70% of patients in double-blind placebo-controlled trials. Guanabenz (16 to 64mg) produced a similar response rate. The most frequent side effects of guanabenz were drowsiness, dry mouth, dizziness and weakness, and such effects may lead to discontinuation of therapy in some patients [1].

参考文献:
[1] Holmes B, Brogden R N, Heel R C, et al.  Guanabenz[J]. Drugs, 1983, 26(3): 212-229.
[2] Aantaa R, Marjam ki A, Scheinin M.  Molecular pharmacology of α2-adrenoceptor subtypes[J]. Annals of medicine, 1995, 27(4): 439-449.
[3] Rmer L, Wurster S, Savola J M, et al.  Identification and characterization of the imidazoline I2b-binding sites in the hamster brown adipose tissue as a study model for imidazoline receptors[J]. Archives of physiology and biochemistry, 2003, 111(2): 159-166.