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They are mainly used in research, having found limited clinical application in human medicine. They are extensively used in veterinary medicine to reverse the effects of alpha-2 agonist drugs used as sedatives, like xylazine, medetomidine and dexmedetomidine. Alpha-2 blockers increase noradrenaline release.
The alpha-2 (α 2) adrenergic receptor (or adrenoceptor) is a G protein-coupled receptor (GPCR) associated with the G i heterotrimeric G-protein. It consists of three highly homologous subtypes, including α 2A-, α 2B-, and α 2C-adrenergic. Some species other than humans express a fourth α 2D-adrenergic receptor as well. [1]
Alpha-adrenergic agonists are a class of sympathomimetic agents that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α 1 and α 2. Alpha 2 receptors are associated with sympatholytic properties. Alpha-adrenergic agonists have the opposite function of alpha blockers.
Medetomidine is a racemic mixture of two optical or stereoisomers, levomedetomidine and dexmedetomidine. [4] The latter causes the alpha 2- adrenergic agonist effects. [5] It is often used as the hydrochloride salt, medetomidine hydrochloride, a crystalline white solid that can be administered as an intravenous drug solution with sterile water.
Instead of treating diseases, they are used as antidotes for reversing overdose of alpha-2 agonist, reducing the toxic effect of the agonist. [4] Only limited indications are present for this drug. More research is in progress to investigate the possible use of alpha2 blockers.
Dexmedetomidine is a highly selective α 2-adrenergic receptor agonist. It possesses an α 2:α 1 selectivity ratio of 1620:1, making it 8 times more selective for the α 2-adrenergic receptor than the related drug clonidine.
Xylazine is a potent α 2-adrenergic receptor agonist. [23] [3] When xylazine and other α 2-adrenergic receptor agonists are administered, they distribute throughout the body within 30 to 40 minutes. [17]
They inhibit the release of circulating adrenergic neurotransmitters like norepinephrine, which contributes to the contraction of smooth muscles. [2] Examples of alpha 2 blockers include yohimbine and idazoxan. [2] Apart from being used as antidotes to reverse the overdose effects of alpha 2 agonists, they only have a limited number of ...