Alpha1 receptor antagonists (selective)

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

alpha1 receptor antagonist; alpha1 receptor blocker; alpha1-receptor blockers; Alpha1-Sympatholytic; Selective alpha1 receptor antagonists; Selective alpha1 receptor blockers; α1-adrenoceptor antagonists; α1 receptor antagonists

Definition
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Selective α1 receptor antagonists act as competitive antagonists at the α1 receptors. The effect of adrenaline and noradrenaline is thereby cancelled. The active ingredients are used as second-choice agents in hypertension.

Antagonization of α1 receptors lowers peripheral resistance and blood pressure. The antagonization of presynaptic α2 receptors interrupts the important control circuit for the exocytotic release of noradrenaline. The only substance that inhibits α1 and α2 receptors in therapeutic doses is phenoxybenzamine. For pharmacotherapy, however, only therapy with selective alpha1-receptor antagonists has become established. Non-selective α receptor antagonists have become practically irrelevant (Graefe KH et al. 2016).

The following substances are classified as selective alpha1-receptor antagonists

Urapidil also has an agonistic effect on serotonin receptors (5-HT1A). It is important to note that receptor antagonists can only act if the corresponding receptor is tonic-activated. However, this state is true for the alpha1-receptors of the resistance vessels. Thus they act as blood pressure reducers.

General information
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Adrenoreceptors of the alpha type, alpha receptors for short, are subdivided into alpha1 and alpha2 receptors. There are 3 subtypes of both alpha-receptor types:

  • α1A receptor
  • α1B- Receptor
  • α1D- Receptor

The alpha1-adrenoreceptors belong to the adrenoceptors (see below G-protein coupled receptor) and are detectable mainly in the presynaptic membrane of sympathetic and also parasympathetic neurons, but also on the cell membrane of adipocytes. They are activated by accumulation of catecholamines (adrenalin and noradrenalin).

α 1-adrenoreceptors contribute to the regulation of sympathetic nervous system activity and influence a number of sympathetic responses, for example to smooth muscle in vessels, bronchial tubes, hair follicles (goose bumps), the urogenital tract and the gastrointestinal tract. They unfold their effect via the Gq protein (see below G-protein coupled receptors , see also adrenoceptors). This leads to an activation of the phospholipase C (type β). This lipase cleaves membrane lipids such as phosphatidylinositol-4,5-bisphosphate (PIP2) to diacylglycerol (DAG) and inositoltrisphosphate (IP3).

The α2 adrenoceptors can be further subdivided into α2B/D, α2B and α2C receptors.

  • α2A- Receptor
  • α2B- Receptor
  • α2C- Receptor

Due to the lack of selective antagonists, the subtypes of both receptor types are not precisely characterized. It is known that theα1A receptor subtype mediates vasoconstriction, theα1B receptor subtype causes the known positive inotropic effect at the heart of theα1 receptor.

The vasoconstriction mediated by the presynapticα2 receptor is mediated by theα2B receptor. The activation of the α2C-receptor leads to the activation of a Gi-protein (= inhibitory G-protein) which inhibits the adenylate cyclase (AC) and thus leads to a reduction of the cAMP levels. The antagonization of α1-receptors lowers the peripheral resistance and blood pressure. The antagonization of presynapticα2 receptors interrupts the important control loop for the exocytotic release of noradrenaline.

The only substance that inhibitsα1 andα2 receptors in therapeutic doses is phenoxybenzamine.

For pharmacotherapy, however, only therapy with selective alpha1-receptor antagonists has become established. Non-selective α receptor antagonists have become practically irrelevant (Graefe KH et al. 2016).

Therapy
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Arterial hypertension (in this indication, however, they do not belong to the first-line therapy)

Raynaud's syndrome: Prazosin is the main drug used in this indication

Benign prostatic hyperplasia (prazosin, alfuzosin, tamsulosin). Alpha1-receptor antagonists can reduce muscle tone in the bladder neck.

Contraindicated are alpha1-receptor antagonists in pregnancy and lactation, in heart failure and in children <12 years of age.

Literature
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  1. Graefe KH et al. sympathetic nervous system. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart p.99

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Last updated on: 29.10.2020