Disease relevance of xylazine

• This study examined whether this reflected vascular changes and, because xylazine induces hyperglycemia, whether glucose could cause similar vascular effects in cerebral ischemia [1].
• METHODS: Lewis lung carcinoma (LLC) cells and cardiomyoblasts were treated for 2 h with a 100 micromol/L concentration of xylazine, ketamine, xylazine plus ketamine (Xy/Ke), or pentobarbital and were measured for (18)F-FDG uptake [2].
• In another experiment with cats divided into two groups according to motion sickness susceptibility, s.c. administration of yohimbine effectively antagonized the xylazine-induced emesis in both susceptibility groups [3].
• The possible role of the alpha-2 adrenoceptors in xylazine-induced vomiting and in motion sickness was investigated [3].
• Clonidine and xylazine injected intraperitoneally both produced a dose-dependent hypothermia in unanaesthetized, freely moving rats [4].

Psychiatry related information on xylazine

• Decreased pain was correlated with increased motor activity for morphine and amphetamine, and with decreased activity for xylazine and acepromazine; dipyrone and indomethacin did not alter activity levels [5].
• The stimulus generalization gradient of xylazine was established each time the animals had reached criterion on successive training doses; the criterion required that lever selection be appropriate to the saline or xylazine injection on 10 consecutive sessions [6].
• Xylazine in human tissue and fluids in a case of fatal drug abuse [7].
• Xylazine provided the highest pain threshold for the first 60 minutes and a sedative effect for 105 minutes [8].
• Low doses of xylazine (0.1-0.2 mg/kg) decreased reaction times while clearly sedative doses (10 mg/kg) had no effect [9].

High impact information on xylazine

• While studying single trial variability and state-dependent modulation of evoked responses in auditory cortex of ketamine/xylazine-anesthetized rats, we have observed an apparent violation of this model [10].
• We observed an induction of basic fibroblast growth factor (bFGF) mRNA in the rat retina after systemic administration of the alpha 2-adrenergic agonists xylazine and clonidine [11].
• However, a nonspecific lipid binding reagent, xylazine, does not affect adipocyte differentiation or mitotic clonal expansion [12].
• On reperfusion, ischemic cerebral blood flow with xylazine/ketamine anesthesia was approximately half that with pentobarbital [1].
• BACKGROUND AND PURPOSE: A well-demarcated infarct was observed after 4 hours of rat middle cerebral artery (MCA) occlusion with xylazine/ketamine but not pentobarbital or isoflurane anesthesia [1].

Chemical compound and disease context of xylazine

• Ketamine/xylazine anesthesia caused marked hyperglycemia and was not further evaluated [13].
• An alpha 2-adrenergic blocking agent, yohimbine, and an alpha 1- and alpha 2-adrenergic blocking agent, phentolamine, at 500 micrograms/kg each reduced or abolished xylazine-induced hyperglycemia and hypoinsulinemia [14].
• Both detomidine and xylazine caused dose-dependent mydriasis in anaesthetized rats, detomidine being about 10 times more potent than xylazine [15].
• Three cats, anesthetized with xylazine and pentobarbital sodium and prepared with acute tracheostomy and femoral arterial catheter, and three awake cats, prepared with a small tracheal catheter and femoral arterial catheter, were subjected to acute hypercapnia (FICO2 = 0.00, 0.06, and 0.08) [16].
• Concentrations of adenosine and its purine nucleoside metabolites inosine, hypoxanthine, and xanthine in the retina-choroid of ketamine/xylazine-anesthetized rats were measured during retinal ischemia using high performance liquid chromatography [17].

Biological context of xylazine

• During ketamine/xylazine anesthesia in rats we performed ultrasound arterial wall tracking and invasive pressure measurements to determine, at the level of the thoracic aorta, diastolic pressure, diastolic lumen area, changes in pressure and lumen area during the cardiac cycle, and indexes of compliance and distensibility [18].
• Xylazine is a tranquilizer that is widely used in both biomedical research and veterinary medicine [19].
• Xylazine induced ERK phosphorylation at 1 mg/kg and reached a maximum at 10 mg/kg [20].
• CONCLUSION: Xy/Ke anesthesia markedly elevates blood (18)F-FDG activity and reduces tumor uptake ratios through inhibition of insulin release in mice kept fasting 4 h, whereas pentobarbital induces a similar but less severe response through insulin resistance [2].
• All drugs were administered i.v. Methoxamine (3-100 mu/kg) or xylazine (3-300 micrograms/kg) produced a sustained increase in mean arterial pressure but almost no effect on heart rate [21].

Anatomical context of xylazine

• Promoting effects of xylazine on development of thyroid tumors in rats initiated with N-bis(2-hydroxypropyl)nitrosamine and the mechanism of action [22].
• Under ketamine/xylazine anesthesia, we found that repetitive stimulation of subiculum or Schaffer collaterals facilitated entorhinal responses, such that a population spike appeared in layer III [23].
• The present study suggests that xylazine-induced hyperglycemia and hypoinsulinemia are mediated by alpha 2-adrenergic receptors, possibly in beta-cells of pancreatic islets which inhibit the release of insulin [14].
• We examined, in anaesthetized (ketamine/xylazine) rats, the properties of motoneurones with axons in the tibial nerve, from rats performing daily spontaneous running exercise for 12 weeks in exercise wheels ('runners') and from rats confined to plastic cages ('controls') [24].
• Responses indicating reentrance in the dentate gyrus were not found under ketamine/xylazine anesthesia, but were readily evoked under urethane anesthesia [23].

Associations of xylazine with other chemical compounds

• METHODS--Transgenic mice of strain Tg HS/SF-218, carrying human SOD-1 genes, and nontransgenic littermates were anesthetized with chloral hydrate (350 mg/kg IP) and xylazine (4 mg/kg IP) [25].
• Awake IOPs were determined using a TonoPen (Mentor, Norwell, MA) immediately before induction of anesthesia by either isoflurane, ketamine, or a mixture of injectable anesthetics (xylazine, ketamine, and acepromazine) [26].
• The effects of xylazine, a sedative that is extensively used in veterinary medicine, on glucose-stimulated insulin release have been studied using isolated perifused rat pancreatic islets [27].
• Blood-aqueous barrier breakdown was inhibited by indomethacin and ketamine/xylazine anesthesia mixtures, but not by [D-Trp2,D-Pro7,9]-substance P [28].
• Insulin-related changes in the subcellular distribution of insulin receptors in intact rat liver: effects of acute hypoinsulinemia induced by diazoxide, somatostatin, and xylazine [29].

Gene context of xylazine

• To test this hypothesis, male rats (250-290 g) were anesthetized with ketamine/xylazine (which does not alter pulsatile GH secretion) and infused i.v. with a GHRH analog ([des-NH2Tyr1,D-Ala15]hGRF-(1-29)-NH2; 10 microg/h) or saline for 4 h [30].
• We show that STAT3 is activated in the retina after exposure to subtoxic bright light, mechanical trauma, and systemic administration of the alpha(2)-adrenergic agonist xylazine, all of which have been shown previously to condition photoreceptors to resist light-induced degeneration [31].
• Midazolam, a CYP3A probe for both rats and humans, was administered orally (2.7 mg), intravenously (0.57 mg), or via the portal vein (0.57 mg) to rats 4 h after anesthesia with ketamine/xylazine and surgery for placement of indwelling vascular and duodenal catheters and 3 days after surgery (chronic) [32].
• There was no significant increase in serum GH concentration in either group of Pomeranians after xylazine or human GH-releasing factor (GHRF) administration, whereas control dogs had significant (P less than or equal to 0.05) increase in serum GH concentration after administration of either agent [33].
• AIMS: The aims of the present study were to characterise the renal effects of the alpha2-adrenergic agonist, xylazine, in the rat and to test the role of changes in glomerular filtration rate, glucosuria, and arginine vasopressin (AVP) in its mechanism of action [34].

Analytical, diagnostic and therapeutic context of xylazine

• RESULTS: Intramuscular injection of 6 mg/kg xylazine induced an increase in ERK phosphorylation in the retina within 30 minutes that lasted 3 hours [20].
• Intravenous injection of xylazine (15-150 micrograms/kg) induced a dose-dependent hyperglycemia and hypoinsulinemia for 3-4 h [14].
• Subsequently, the impact of (a) fasting for 8-12 h, (b) warming the animals with a heating pad (30 degrees C), and (c) general anesthesia using isoflurane or ketamine/xylazine on the (18)F-FDG biodistribution was evaluated [13].
• Several agents (nitrous oxide, procaine, and xylazine) are not recommended because of poor analgesia [35].
• 3. Xylazine (1-100 micrograms kg-1) inhibited in a dose-dependent manner the tachycardia induced by continuous electrical stimulation (0.2 Hz, 2 ms, 60 V) of the spinal cord (C7-Thl) [36].

References