Interest of α2-Adrenergic Agonists and Antagonists in Clinical Practice: Background, Facts and Perspectives

Abstract

The family of alpha(2)-adrenergic receptors (alpha(2)-ARs) comprises three subtypes which are each endowed with specific functions. alpha(2)-agonists and alpha(2)-antagonists are part of the clinician armamentarium since several decades; however, none of the compounds so far available is subtype selective. For long, clonidine and yohimbine have been used for the treatment of hypertension and impotence respectively, but both have been superseded by newer drugs. This review attempts, by a comprehensive analysis of the literature, to cover the present clinical use and the potential therapeutic interest of alpha(2)-agonists or antagonists. From the clinical data, it is concluded that, with the exception of a few particular situations, alpha(2)-agonists are only of limited utility as a monotherapy. By contrast, they offer several powerful advantages when used in adjunctive therapy. In perioperative settings, alpha(2)-agonists are extremely valuable adjuncts to anesthetics and analgesics for the induction of anxiolysis, maintenance of sedation, management of pain and prevention of shivering. In the ophthalmic clinic, they are used to lower intra-ocular pressure during laser surgery of the eye. As a daily medication, alpha(2)-agonists are also of interest for the treatment of glaucoma, muscle spasticity, opiate withdrawal, and behavior disorders. The alpha(2)-antagonists are useful antidotes for reversing the threatening effects of agonist overdose, but currently there are very few indications. New applications are under investigation, and new molecules with more refined subtype-selectivity may emerge, so the clinical utility of both alpha(2)-agonists and antagonists will undoubtedly expand in the future.

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

“…Our results also showed that the site of action is presumably within the CNS [16,17], where the activation of α2B-and α2C-ARs initiates a chain of events resulting in vagally mediated release of mucosal protective factors, such as prostaglandins and nitric oxide [13,16]. Because α2-AR agonists are widely used as antihypertensive drugs, as adjuncts to anesthetics and analgesics during the perioperative period, or as drugs to treat opiate withdrawal or attentiondeficit/hyperactivity disorder [50], a potential anti-ulcer effect is of high clinical relevance.…”

Clonidine versus Tramadol for postanesthetic shivering: a randomized clinical trial study

“…Complications of clonidine consumption are usually mild. Due to their anti-anxiety effects, alpha-2 agonists are good supplements for anesthetics and analgesics (Crassous et al, 2007;Moodi and Borjian, 2009). Also, other studies have shown that tramadol is a new synthetic opioid with characteristics of a receptor μ antagonist; it can inhibit the uptake of norepinephrine, dopamine and serotonin in the central nervous system.…”

α2‐Agonists as analgesic agents

“…[70][71][72][73][74][75] Moreover, a 2 -agonists are widely used in veterinary anesthesia and analgesia. This review will now consider both a 2 -agonists currently used in pain therapy and emerging novel molecules which have shown significantly reduced side-effects with respect to the older a 2 -agonists, providing an outline of the open and, in particular, patent literature.…”