Xylazine is a structural analog of clonidine and an α<sub>2</sub>-adrenergic receptor agonist, sold under many trade names worldwide, most notably the Bayer brand name Rompun, In veterinary anesthesia, it is often used in combination with ketamine. Veterinarians also use xylazine as an emetic, especially in cats. Drug interactions vary with different animals.
Xylazine was first investigated for human use in the 1960s in West Germany for antihypertensive effects before being discontinued and marketed as a veterinary sedative. Xylazine’s mechanism of action was discovered in 1981, which led to the creation of other α<sub>2</sub>-adrenergic receptor agonists such as medetomidine and dexmedetomidine.
Xylazine has become a commonly abused street drug in the United States where it is known by the street name "tranq", particularly in the territory of Puerto Rico. The drug is used as a cutting agent for heroin and fentanyl.
History
Xylazine was discovered as an antihypertensive agent in 1962 by Farbenfabriken Bayer in Leverkusen, West Germany. In human trials xylazine was found to depress the central nervous system leading to the discontinuation of further research for its use in humans and it was instead marketed as a veterinary sedative. Xylazine was first used for this purpose in the late 1960s. Xylazine proved popular and in the 1970s became one of the most common large animal sedatives.
In scientific research using animal experiments, xylazine is a component of the most common anesthetic, ketamine-xylazine , to anesthetize rats, mice, hamsters, and guinea pigs.
Xylazine has not previously been a controlled substance; however, due to illicit abuse of xylazine legislative restrictions have been proposed in multiple countries.
Veterinary use
thumb|As a veterinary anesthetic, xylazine is administered once for intended effect before surgical procedures (trade name: Rompun)
Xylazine is widely used in veterinary medicine as a sedative, muscle relaxant, and analgesic. It is frequently used in the treatment of tetanus. In animals, xylazine may be administered intramuscularly, intravenously, and intraosseously. Subcutaneous, oral transmusocal and intranasal have been investigated but are not standard routes for xylazine administration. Xylazine is licensed for use in non-meat horses. Off-label use in cattle is common with recommended withholding periods of 1–5 days for dairy cattle and 4–10 days for meat cattle. Cattle are more sensitive to xylazine than horses with the sensitivity being greater in meat cattle breeds than dairy cattle breeds.
Xylazine administration in sheep activates pulmonary macrophages that damage the capillary endothelium and alveolar type I cells. This in turns causes alveolar haemorrhage and oedema causing hypoxaemia.
Intracarotid administration can cause seizures and excitement in horses. The renal threshold for glucose is not exceeded due to the hyperglycaemia with clinical doses. An alpha<sub>2</sub> adrenergic receptor antagonist can reverse the effect.
Pharmacokinetics
In animals
In dogs, sheep, horses, and cattle, the half-life is very short: only . Complete elimination of the drug can take up to 23minutes in sheep and up to 49minutes in horses. In non-fatal cases, the blood plasma concentrations range from 0.03 to 4.6 mg/L. Around 70% of a dose is excreted unchanged.
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Xylazine is a potent α<sub>2</sub>-adrenergic receptor agonist. Recent data suggests that xylazine treatment can induce dopamine release in the nucleus accumbens through an unresolved mechanism, and this effect is blocked by atipamezole.
Xylazine also serves as a transport inhibitor by suppressing norepinephrine transport function through competitive inhibition of substrate transport. Accordingly, xylazine significantly increases K<sub>m</sub> and does not affect V<sub>max</sub>.
Unlike other α<sub>2</sub>-adrenergic receptor agonists xylazine does not have any imidazoline receptor activity. Xylazine binds at a ratio of 160:0, the lowest of all α<sub>2</sub>-adrenergic receptor agonists and 1/10th of that of medetomidine and dexmedotimidine.
Xylazine is not regulated as a controlled substance under the Controlled Substances Act. It is sold online through distributors often without requiring proof of a veterinary license. As a commonly used veterinary medicine xylazine is probably diverted from veterinary sources. The cost to purchase Xylazine from overseas suppliers is around $6–20 per kilogram. This low price makes it attractive for dealers looking for a cheap additive that is addictive and not treatable with opiate withdrawal medications. The withdrawal can last for two weeks and has a quicker onset than fentanyl.
As an adulterant, xylazine is most commonly ingested with fentanyl. Xylazine has also been reported in combination with medetomidine, another potent α<sub>2</sub>-adrenergic receptor agonist. It is unknown if drug users are ingesting it knowingly. As of 2024, Seattle police report that some users wrongly believe they are consuming higher-quality fentanyl. Xylazine's street name in Puerto Rico is anestesia de caballo, which translates to "horse anesthetic". From 2002 to 2008, its use was associated with a high number of inmate deaths at the Guerrero Correctional Institution in Aguadilla, Puerto Rico.
Xylazine's street name in the United States, particularly when it is mixed with fentanyl, is "tranq", "tranq dope" and "zombie drug".
As of 2012, xylazine users in Puerto Rico were more likely to be male, under age 30, living in a rural area, and injecting rather than inhaling xylazine. The combination of heroin and xylazine produces a potentially more deadly high than administration of heroin alone. Xylazine is also frequently found in "speedball", a mixture of a stimulant drug such as cocaine with a depressant drug such as heroin, morphine and/or fentanyl. From November 2021 until August 2022, 80% of drug paraphernalia which tested positive for fentanyl at needle exchange programs in Maryland also contained xylazine. As of 2022, xylazine was almost invariably combined with opioids when used recreationally, and the drug produced a characteristic withdrawal syndrome which complicates treatment of addicted users.
In April 2023, the Biden administration declared xylazine-laced fentanyl an official emerging drug threat to the nation, the first time such a label has been given. In 2022, the Drug Enforcement Administration (DEA) reported that 23% of seized fentanyl powder and 7% of fentanyl pills were found to have been adulterated with xylazine.
Side effects
Xylazine overdose is often fatal in humans. Xylazine significantly decreases heart rate in animals that are not pre-medicated with medications that have anticholinergic effects.
, the α<sub>2</sub>-adrenergic receptor antagonist atipamezole was used to reverse the effects of xylazine or the related drug dexmedetomidine in veterinary medicine, but this is not an approved medical treatment for humans, despite Phase I clinical trials in 2005.
the effects of xylazine in animals were also reversed by the analeptics 4-aminopyridine, doxapram, and caffeine, which are physiological antagonists to central nervous system depressants. The ways to accurately identify chronic xylazine usage are unknown, and the effective treatments, if any, are not standardized. multiple drugs have been used for therapeutic intervention, including lidocaine, naloxone, thiamine, lorazepam, vecuronium, etomidate, propofol, tolazoline, yohimbine, atropine, orciprenaline, metoclopramide, ranitidine, metoprolol, enoxaparin, flucloxacillin, insulin, and irrigation of both eyes with saline.