Antagonistic effect of atipamezole on xylazine-induced sedation, bradycardia, and ruminal atony in calves.

Three doses of an alpha 2-adrenoreceptor antagonist, atipamezole, were administered to reverse xylazine-induced sedation, bradycardia, and ruminal atony in calves. Once a week for 4 weeks, each of 6 calves was administered IV 1 treatment of: 0.3 mg of xylazine/kg of body weight, followed in 10 minutes by 1 ml of 0.9% NaCl; 0.3 mg of xylazine/kg, followed in 10 minutes by 3 micrograms of atipamezole/kg; 0.3 mg of xylazine/kg, followed in 10 minutes by 10 micrograms of atipamezole/kg; or 0.3 mg of xylazine/kg, followed in 10 minutes by 30 micrograms of atipamezole/kg. The order of the 4 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 33.6 +/- 7.1 minutes (mean +/- SEM). Atipamezole administered at dosages of 3, 10, and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 20.5 +/- 3.0, 10.2 +/- 0.2, and 9.3 +/- 0.5 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Atipamezole given at 3, 10, and 30 micrograms/kg shortened the time from onset of lateral recumbency to standing to 40.2 +/- 6.9, 12.8 +/- 1.1, and 10.0 +/- 0.7 minutes, respectively. Drowsiness was found in calves given the lowest dosage of atipamezole (3 micrograms/kg) after the calves stood. Atipamezole given at dosages of 10 and 30 micrograms/kg reversed xylazine-induced ruminal atony in a dose-dependent manner. In addition, 30 micrograms of atipamezole/kg reversed xylazine-induced bradycardia, but the lower dosages of this antagonist did not. Results indicated that 30 micrograms of atipamezole/kg should be a useful antidote for xylazine overdose in cattle.     

Antagonistic effects of atipamezole,yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α₂-adrenoceptors but not α₁-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.     

Evidence for the involvement of alpha 2-adrenoceptors in the emetic action of xylazine in cats

Intramuscular injection of xylazine induced dose-dependent vomiting in cats (ED50 = 0.277 mg/kg); administration of standard dose of xylazine (2 mg/kg, 2 times the 100% emetic dose) induced vomiting in 100% of the cats studied. The xylazine-induced vomiting was antagonized by adrenoceptor antagonists possessing alpha 2-blocking activity, which were yohimbine, tolazoline, and phentolamine. Of these antagonists, yohimbine was the most effective; the maximal antagonistic effect was seen at 1 mg of yohimbine/kg, a dose at which the other drugs had little or no effect. At the doses studied, prazosin and phenoxybenzamine, adrenoceptor antagonists with alpha 1-blocking activity, did not prevent vomiting induced by xylazine. Beta-Adrenoceptor (propranolol), dopamine receptor (domperidone and chlorpromazine), a cholinoceptor (atropine), an opiate receptor (naloxone), and a histamine-receptor (diphenhydramine) antagonists, at the doses studied, did not prevent xylazine-induced vomiting. Pretreatment with 6-hydroxydopamine failed to prevent xylazine-induced vomiting. These results indicated that xylazine-induced vomiting in cats is mediated by alpha 2-adrenoceptors and suggested that the alpha 2-adrenoceptors mediating the vomiting attributable to xylazine may not be presynaptic alpha 2-receptors located on noradrenergic nerve terminals.     

Reversal of xylazine-induced sedation in dairy calves with atipamezole: A field trial

Dairy calves immobilized with xylazine (XYL) were given atipamezole-HCl (ATI) at different XYL:ATI dose ratios (w/w) for reversal and the antagonistic effect of xylazine was evaluated. Control animals received saline for comparison. Intramuscular administration of xylazine (0.139–0.357 mg/kg) induced sedation with complete immobilization in all animals (n=195) and there were no spontaneous recoveries before injection of atipamezole or saline. Atipamezole was given 10–81 min and saline 25 min after xylazine administration. Intramuscular administration of atipamezole at XYL:ATI dose ratios of 5:2 (n=11), 10:3 (n=21), 4:1 (n=21) and 5:1 (n=25) effectively antagonized the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 6.09 (3.12), 5.15 (2.87), 6.35 (2.54) and 7.86 (3.11) min, respectively. The mean time to standing for control animals (n=11) was 94.1 (3.0) min. Intravenous administration of atipamezole at XYL:ATI dose ratios of 10:3 (n=7), 4:1 (n=33), 5:1 (n=16), 8:1 (n=27) and 10:1 (n=9) rapidly reversed the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 0.98 (0.22), 1.32 (0.48), 1.09 (0.34), 1.39 (0.52) and 1.60 (0.69) min, respectively. The mean time to standing for control animals (n=14) was 88.1 (13.1) min.Animals given high doses of atipamezole (dose ratio groups 5:2 intramuscularly, 10:3 intravenously and 4:1 intravenously) showed signs of excitement while in animals given low doses of atipamezole (dose ratio groups 5:1 intramuscularly and 10:1 intravenously) resedation and relapse into recumbency occurred. Medium doses of atipamezole (dose ratio groups 10:3 intramuscularly, 4:1 intramuscularly, 5:1 intravenously and 8:1 intravenously) did not cause any undesirable side-effects or resedation, and can be recommended for reversal of xylazine-induced sedation in dairy calvesAbbreviations ATI atipamezole-HCl - BW body weight - IM intramuscular - IV intravenous - SD standard deviation - XYL xylazine     

Antagonistic effects of alpha-adrenoceptor blocking agents on reticuloruminal hypomotility induced by xylazine in cattle.

The intravenous injection of a standard dose (0.05 mg/kg) of xylazine inhibited reticuloruminal motility in cattle. Pretreatment with adrenoceptor antagonists showing alpha 2-blocking activity, tolazoline (0.5 mg/kg) and yohimbine (0.2 mg/kg), antagonized the xylazine-induced reticuloruminal amotility. Tolazoline was more effective than yohimbine, since an antagonistic effect was not seen at 0.5 mg/kg yohimbine, and yohimbine at 0.2 mg/kg was less effective than tolazoline at 0.5 mg/kg. An adrenoceptor antagonist showing alpha 1-blocking activity, prazosin, did not prevent the inhibition of reticuloruminal motility by xylazine. The xylazine-induced reticuloruminal amotility was also not prevented by either a dopamine receptor antagonist, domperidone, or an opiate receptor antagonist, naloxone. These results suggest that xylazine inhibits bovine reticuloruminal motility through its activation of alpha 2-adrenoceptors, and show that tolazoline can be used as a specific antagonist of xylazine in studies of the alpha-adrenergic influence on reticuloruminal motility in cattle.     

The effect of xylazine on the isolated sheep trachea

The effect of xylazine on the isolated sheep trachea and its possible interactions with the α₂-adrenergic antagonist, atipamezole, and the anticholinergic agent, atropine, was studied. The mechanical responses of the tracheal preparations were recorded after exposing each one to cumulatively increasing concentrations of xylazine alone or in the presence of atipamezole or atropine.
Xylazine exerted a concentration-dependent contractile effect, with a threshold concentration of 10^--⁷M while the maximum activity was produced at a concentration of 10^--⁵M (EC₅₀= 2.3 × 10^--⁷). This xylazine-induced contractile effect was inhibited by atipamezole, but not significantly modified by atropine. Thus, it is concluded that α₂-adrenoceptors exist in the sheep trachea and it is suggested that α₂-adrenoceptor agonists may act on airways in sheep directly through stimulation of peripheral α₂-adrenergic receptors and indirectly via central α₂-adrenergic receptor activation of parasympathetic tone.     

Influence of nifedipine on xylazine-induced acute pressor response in halothane-anesthetized dogs

Effects and interaction of nifedipine (Ca channel blocker) and xylazine (mixed alpha agonist) during halothane anesthesia were examined in 6 dogs. After achievement of steady-state halothane (1.35%) anesthesia, blood pressure (BP) and heart rate (HR) were recorded in these dogs during 3-minute saline or nifedipine (20 micrograms/kg) infusion periods. Seven minutes after the end of saline or nifedipine infusion, xylazine (1.1 mg/kg of body weight) was infused over a 2-minute period. After saline pretreatment, xylazine administration increased diastolic BP (33.67 +/- 3.91 mm of Hg) and decreased HR. Nifedipine infusion induced a transient reduction in BP, accompanied by a more persistent increase in HR. Compared with saline pretreatment, nifedipine pretreatment significantly decreased the acute increase in diastolic BP (33.67 +/- 3.91 vs 14.00 +/- 2.94 mm of Hg) which occurred during xylazine injection. After saline and nifedipine infusions, xylazine administration decreased HR 30 +/- 15.02 and 36.5 +/- 10.36 beats/min, respectively. A pronounced sinus arrhythmia and/or 2nd-degree atrioventricular block developed in all dogs during xylazine injection after saline infusion. Arrhythmias were not observed in the dogs after nifedipine infusion. Nifedipine's Ca blocking action depressed xylazine-induced acute vasoconstriction and concomitant increase in diastolic BP. Because alpha 2-, but not alpha 1-adrenoceptor-mediated vasoconstriction is Ca-dependent, these results indicate that a portion of the acute pressor response induced by IV xylazine in halothane-anesthetized dogs may be alpha 2-mediated. Seemingly, nifedipine-induced hypotension and damping of xylazine-induced increases in BP attenuated xylazine's actions on cardiac rate and rhythm.     

Influence of tolazoline on caudal epidural administration of xylazine in cattle

Eight adult female cattle (6 Holstein, 1 Jersey, 1 Brown Swiss) were used to determine the antagonistic effects of tolazoline, and alpha 2-adrenoceptor antagonist, on xylazine-induced (via caudal epidural administration) depression of CNS, respiratory, and cardiovascular activity and rumen motility. A 2% solution of xylazine HCl was injected into the epidural space at the first coccygeal interspace, using a dosage of 0.05 mg/kg of body weight, diluted to a 5-ml volume with sterile water, and administered at a rate of approximately 1 ml/30 s. Eight minutes after xylazine injection, either tolazoline (0.3 mg/kg) or saline solution (4 ml) was administered IV. All 8 cattle were treated, using both regimens in a random sequence; at least 1 week elapsed between treatments. Epidurally administered xylazine induced caudal analgesia (S3 to coccyx), as evaluated by no response to superficial and deep muscular pinprick, and induced sedation, cardiopulmonary depression, and inhibition of rumen motility, but all cattle remained standing. Tolazoline effectively reversed xylazine-induced rumen hypomotility, and partially antagonized xylazine-induced cardiopulmonary depression without affecting sedation and desirable local (S3 to coccyx) analgesic effects.     

Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4±0.1 mg/kg; mean ±SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4±1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2±0.4°C, 75.5±6.5 beats/min and 62.1±4.2 breaths/min, respectively.All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8±4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41±0.58 min.Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.Abbreviations i.m. intramuscular(ly) - i.v. intravenous(ly) - SEM standard error of the mean     

Effect of xylazine on heart rate and arterial blood pressure in conscious dogs, as influenced by atropine, 4-aminopyridine, doxapram, and yohimbine

The effects of xylazine on heart rate (HR) and mean arterial blood pressure (ABP) were studied in 5 conscious male dogs. An IV injection of xylazine (1 mg/kg) caused a decrease in HR, which was accompanied by sinus arrhythmia. Xylazine administration also caused an initial increase in ABP, which was followed by a decrease. Atropine sulfate (0.045 mg/kg, IM) increased both the ABP and HR, but prevented xylazine-induced bradycardia only in 3 of 5 dogs. The other 2 dogs had to be given a supplemental dose of atropine sulfate (0.01 mg/kg, IV) before xylazine-induced bradycardia was antagonized. In addition, atropine sulfate potentiated xylazine-induced hypertension for 60 minutes. Yohimbine, an alpha 2-adrenoreceptor blocking agent, given IV at a dosage of 0.1 mg/kg, antagonized hypertension, hypotension, and bradycardia induced by xylazine. In addition, doxapram HCl, given IV at a dosage of 5.5 mg/kg, antagonized bradycardia but potentiated xylazine-induced hypertension, and an IV injection of 4-aminopyridine at a dosage of 0.5 mg/kg did not affect the cardiovascular actions of xylazine. It was concluded that atropine sulfate at the IM dosage of 0.045 mg/kg may be insufficient to antagonize xylazine-induced bradycardia but may potentiate xylazine-induced hypertension, and yohimbine may be useful in antagonizing these untoward reactions associated with xylazine administration. Doxapram and 4-aminopyridine were not found to be beneficial.     

Antagonistic effect of idazoxan on xylazine-induced central nervous system depression and bradycardia in calves

Two doses of an alpha 2-adrenoreceptor antagonist, idazoxan, were administered to reverse the CNS depressant and bradycardia effects of xylazine in calves. Once a week for 3 weeks, each of 6 calves were administered IV one treatment of: (1) 0.2 mg of xylazine/kg of body weight followed in 10 minutes by 1 ml of 0.9% NaCl, (2) 0.2 mg of xylazine/kg followed in 10 minutes by 10 micrograms of idazoxan/kg, or (3) 0.2 mg of xylazine/kg followed in 10 minutes by 30 micrograms of idazoxan/kg. The order of the 3 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 27.2 +/- 3.0 minutes (mean +/- SEM). Idazoxan administered at dosages of 10 and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 11.5 +/- 0.8 and 10.3 +/- 0.2 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Idazoxan given at dosages of 10 and 30 micrograms/kg shortened the time to standing to 16.8 +/- 1.7 and 11.3 +/- 0.2 minutes, respectively. Idazoxan given at a dosage of 30 micrograms/kg also reversed xylazine-induced bradycardia. Results indicated that idazoxan should be a useful antidote for xylazine overdose in cattle.     

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.     

The effects of alpha2 adrenoceptor agonists on airway pressure in anaesthetized sheep

Xylazine and clonidine, given intravenously, cause an increase in airway pressure in the anaesthetized, ventilated sheep. This increase was dose dependent and was not mediated by histamine, nor was it blocked by the alpha 1-adrenoceptor antagonist prazosin. However, the increase was abolished by the alpha 2-adrenoceptor antagonist, idazoxan. When the alpha 2-adrenoceptor agonists were administered into the cerebrospinal fluid by injection into the cisterna magna there was no increase in airway pressure, although a similar dose given peripherally still produced an effect. These findings would indicate that the increase in airway pressure seen in these sheep, following administration of xylazine and clonidine, was mediated by peripherally located alpha 2-adrenoceptors.     

Immobilising free-ranging Alpine chamois with xylazine, reversed with atipamezole

Between 1996 and 2005, 215 free-ranging Alpine chamois (Rupicapra rupicapra) were immobilised with xylazine hydrochloride. The 110 male and 105 female animals received a mean (sd) dose of 2.5 (0.6) mg/kg with a range from 1.4 to 4.8 mg/kg. The immobilisation was reversed in 201 of the animals with an intramuscular injection of 0.3 (0.1) mg/kg atipamezole (range 0.03 to 0.76 mg/kg), corresponding to a mean ratio of atipamezole:xylazine of 1:9.4 (4.3). All the chamois were immobilised, but shorter induction and recovery times, and deeper sedation with no reactions to handling were obtained in more than 80 per cent of the animals with doses of 2.6 to 3.6 mg/kg of xylazine, reversed with 0.26 to 0.36 mg/kg atipamezole (a ratio of 1:10), injected within 90 minutes.     

The effect of the polymerized bovine haemoglobin solution, Hb-200, on endothelial function in isolated arterial rings from rats

Haemoglobin-based oxygen carriers have been developed as 'blood substitutes'. Early cross-linked haemoglobins caused marked vasoconstriction, however, polymerized haemoglobin solutions, such as the bovine product haemoglobin glutamer-200 (bovine) (Hb-200), are said to have lesser vascular effects. The aim of this study was to quantify the effect of Hb-200 on isolated rat arterial rings. The actions of Hb-200 were investigated using rings of aorta and second-order mesenteric arteries from female Wistar rats. The arterial rings were mounted for isometric tension recording. Addition of Hb-200 (1 microM) to arterial rings, precontracted with phenylephrine (50-70% maximum phenylephrine-induced tone), resulted in vasoconstriction. Addition of Hb-200 to arteries precontracted with phenylephrine and relaxed with acetylcholine (1 microM) also caused contraction. Furthermore preincubation with Hb-200 (1 microM) enhanced the response to phenylephrine (1 nm to 10 microM) and impaired acetylcholine-induced relaxation (10 nm to 10 microM). Responses to Hb-200 were similar to those in response to the nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME, 100 microM), alone or in combination with Hb-200. These data demonstrate that Hb-200 has a significant vasoconstrictor effect similar to L-NAME. Thus the vascular actions of Hb-200 are consistent with activity as a NO scavenger. This may have implications for the clinical use of Hb-200.     

The cardiorespiratory effects of intrathecal xylazine in the conscious rabbit

The alpha 2 agonist xylazine produced a dose-dependent decrease in mean arterial blood pressure in conscious rabbits when injected intrathecally (i.t.) through a cannula previously implanted under general anaesthesia. Intrathecal administration of 200 and 400 micrograms of xylazine produced a significant reduction in arterial blood pressure from control values (maximum depressions of 25% and 33%, respectively). There was little effect on cardiac output and arterial carbon-dioxide tension and no effect on respiratory rate, arterial oxygen tension and pulse rate. Intrathecal injection of 100 microliters of 0.9% saline had no effect. Intravenous (i.v.) tolazoline (0.5 mg/kg) abolished xylazine-induced hypotension (200 micrograms) in four rabbits. Contrast radiography revealed that 100 microliters of solution injected i.t. in anaesthetized rabbits spread distally over eight vertebral spaces. There was little rostral spread. It was concluded that xylazine-induced hypotension following i.t. injection was due to local activation of alpha 2 adrenoceptors present in the thoracic spinal cord. It is postulated that spinal alpha 2 adrenoceptors may play an important role in the hypotension recorded in animals after parenteral injection of xylazine.     

Antagonistic effects of intravenous or epidural atipamezole on xylazine-induced dorsolumbar epidural analgesia in cattle

This study was performed to clarify the antagonistic actions of intravenous or epidural atipamezole on the sedative and analgesic effects of xylazine administered between the epidural fat and dura mater through the first interlumbar space in cattle.Cattle received 5 mL of a solution containing 0.05 mg x kg(-1) xylazine in 0.9% saline. Thirty minutes later, 5 mL of 0.9% saline was administered through the same needle (treatment 1) (XSE). In treatments 2 (XAE) and 3 (XAV), 5 mL of a solution containing 0.025 mg x kg(-1) atipamezole in 0.9% saline was administered epidurally or intravenously, respectively.Sedation and analgesia were similar in all three treatment groups and could be reversed by atipamezole given by either route. In the XAV treatment, the flank area relapsed into analgesia 25+/-5.8 min following reversal of the analgesic effect, and was maintained for 112.5+/-63.8 min.The present study confirmed that the sedative and analgesic effects of xylazine are completely reversed by atipamezole and can be influenced by the epidural fat in cattle. Furthermore, it seems probable that analgesia following epidural administration of xylazine is mediated by alpha(2)-adrenergic receptors, not by a local anaesthetic effect.     

Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep

We compared the ability of tolazoline and yohimbine to antagonize xylazine-induced central nervous system depression, bradycardia, and tachypnea in 9 ewes and 5 rams. Once a week for 3 weeks, each sheep received one IV treatment of 0.4 mg xylazine/kg, 0.4 mg xylazine/kg followed in 10 minutes by 2 mg tolazoline/kg, or 0.4 mg xylazine/kg followed in 10 minutes by 0.2 mg yohimbine/kg. The order of the 3 treatments in each sheep was randomized. Xylazine alone caused recumbency for 41.0 +/- 3.7 minutes (mean +/- SEM). Tolazoline and yohimbine shortened the xylazine-induced recumbency to 12.1 +/- 0.9 minutes and 18.1 +/- 1.5 minutes, respectively. Sheep given xylazine alone had head droop for 34.0 +/- 5.4 minutes after rising. Head drooping of sheep given tolazoline or yohimbine was reduced to 10.1 +/- 1.7 minutes and 14.2 +/- 1.7 minutes, respectively. Both tolazoline and yohimbine reversed the bradycardia and tachypnea that followed xylazine administration. No statistical differences in the rate and magnitude of the reversal were observed between the 2 drugs.     

Pharmacological characterization of alpha1-adrenoceptor subtypes in the bovine tail artery

Ioudina, M. V., Dyer, D. C. Pharmacological characterization of alpha1-adrenoceptor subtypes in the bovine tail artery. J. vet. Pharmacol. Therap. 25, 363-369. The purpose of this study was to identify the alpha1-adrenoreceptor subtypes present in the bovine tail artery which mediate contractions to adrenergic agonists. A61603, an alpha1A-selective agonist, was more potent compared with norepinephrine and phenylephrine. The pKA value of A61603 was 6.93 +/- 0.19 microM (n=6). Antagonists, BMY 7378, WB 4101 and 5-methylurapidil, caused a parallel shift to the right of the concentration-response curve to A61603 with pA2 values of 6.62, 9.27 and 8.86, respectively. Prazosin, BMY 7378 and WB 4101 inhibited phenylephrine induced contraction with pA2 values of 9.47, 7.17 and 9.73, respectively. The pA2 values obtained for 5-methylurapidil, WB 4101, BMY 7378 and prazosin against alpha1-adrenoceptor agonists were significantly correlated with pKi values (Zhu, Zhang & Han, 1997, Eur. J. Pharmacol.329, 55-61) for the cloned alpha1a-adrenoceptor but not with the cloned alpha1b- or alpha1d-adrenoceptor. BMY 7378, a selective alpha1D-adrenoceptor antagonist, was significantly more potent against the nonsubtype selective agonist phenylephrine than to A61603. Chloroethylclonidine (50 microM for 10 min) did not affect contractile responses to A61603, but caused a significant inhibition of contractile responses to phenylephrine. In conclusion, it appears that alpha1A- and alpha1D-adrenoceptors play a role in adrenergic mediated contraction in the bovine tail artery.     

Xylazine-induced mydriasis in rats and its antagonism by α-adrenergic blocking agents

Pupillary response to xylazine (10-300 micrograms/kg, i.v.) norepinephrine (1-30 micrograms/kg. i.v.) and atropine (3-100 micrograms/kg, i.v.) were observed in rats anaesthetized with pentobarbital. Xylazine caused a dose-dependent mydriasis which was antagonized by a selective alpha 2-adrenergic blocking agent, yohimbine (2.5 mg/kg, i.v.). was less effective in antagonizing this effect of xylazine. A selective alpha 1-adrenergic blocking agent, prazosin (2.5 mg/kg, i.v.) was ineffective in reducing the xylazine-induced mydriasis. In contrast, both phentolamine and prazosin blocked the pupillary dilation produced by norepinephrine, while yohimbine was much less effective in antagonizing norepinephrine-induced mydriasis. Atropine also induced a dose-dependent mydriasis which was not affected by yohimbine pretreatment. The present study suggests that the mydriatic effect of xylazine in the rat is mediated by an adrenergic mechanism, possibly by stimulating the alpha 2-adrenergic receptors in the iris and CNS.