Other Alpha-Adrenoceptor Antagonists

OTHER ALPHA-ADRENOCEPTOR ANTAGONISTS

Alfuzosin is anα₁-selective quinazoline derivative that is approvedfor use in BPH. It has a bioavailability of about 60%, is extensively metabolized, and has an elimination half-life of about 5 hours. It may increase risk of QT prolongation in susceptible individuals. Silodosin resembles tamsulosin in blocking theα_1Areceptor andis used in treatment of BPH. Indoramin is another α₁-selective antagonist that also has efficacy as an antihypertensive. It is not available in the USA. Urapidil is anα₁ antagonist (its primary effect) that also has weak α₂-agonist and 5-HT_1A-agonist actions and weak antagonist action at β₁ receptors. It is used in Europe as an antihypertensive agent and for benign prostatic hyperplasia. Labetalol has bothα₁-selective andβ-antagonistic effects; it isdiscussed below. Neuroleptic drugs such as chlorpromazine and haloperidol are potent dopamine receptor antagonists but are alsoantagonists at α receptors. Their antagonism of α receptors prob-ably contributes to some of their adverse effects, particularly hypotension. Similarly, the antidepressant trazodone has the capacity to block α₁ receptors. Ergot derivatives, eg, ergotamine and dihydroergotamine, cause reversible α-receptor blockade, probably via a partial agonist action .

Yohimbine, an indole alkaloid, is anα₂-selective antagonist.It is sometimes used in the treatment of orthostatic hypotension because it promotes norepinephrine release through blockade of α₂receptors in both the central nervous system and the periph-ery. This increases central sympathetic activation and also pro-motes increased norepinephrine release in the periphery. It was once widely used to treat male erectile dysfunction but has been superseded by phosphodiesterase-5 inhibitors like sildenafil . Yohimbine can greatly elevate blood pressure if administered to patients receiving norepinephrine transport blocking drugs. Yohimbine reverses the antihypertensive effects of α₂-adrenoceptor agonists such as clonidine. It is used in veterinarymedicine to reverse anesthesia produced by xylazine, anα₂ agonist used to calm animals. Although yohimbine has been taken off the market in the USA solely for financial reasons, it is available as a “nutritional” supplement.