Medetomidine

"One emerging substance of concern is medetomidine, a racemic mixture of levo- and dex-medetomidine [10]. First identified in the unregulated supply in Maryland in mid-2022 [11], medetomidine, like xylazine, is a potent veterinary tranquilliser; unlike xylazine, its active enantiomer (dexmedetomidine, commonly delivered as injectable Precedex, Pfizer, New York, USA) is an FDA-approved α2-adrenergic agonist used as a sedative, analgesic and anxiolytic in humans. Dexmedetomidine is widely used in hospital settings because it is not a controlled substance and is also used in veterinary medicine and biopharmaceutical research in animal models. Sublingual dexmedetomidine (Igalmi, BioXcel Therapeutics, New Haven, CT, USA) is additionally used in humans for management of agitation among adult patients with agitation due to schizophrenia or bipolar disorder.

"Dexmedetomidine was developed to be a safer human sedative due to its purported lack of respiratory depressive effect and increased selectivity for the alpha-adrenergic receptors. Interestingly, dexmedetomidine and xylazine were both developed in a cascade of medicinal chemistry attempts to improve on the sedative and addiction therapy potential of clonidine, an earlier α2-adrenergic agonist [12]. Xylazine and dexmedetomidine have both been touted as selective α2-adrenergic agonists, but this has recently been refuted for xylazine [13, 14]. In fact, xylazine has now been reported to have agonist activity at the kappa opioid receptor, 5-HT7 serotonin receptor, sigma 1 and 2 receptors, as well as the 3 α2-adrenergic receptor subtypes [13, 14]. Current literature does not report any indications that dexmedetomidine is not selective for the alpha-adrenergic system."