Chemistry - A Rauwolfia or indolealkylamine alkaloid, yohimbine HCl has a molecular weight of 390.9. It is chemically related to reserpine.
Storage/Stability/Compatibility - Yohimbine injection should be stored at room temperature (15-30°C); (Antagonil®-store in refrigerator), and protected from light and heat.
Pharmacology - Yohimbine is an alpha2-adrenergic antagonist that can antagonize the effects of xylazine. Alone, yohimbine increases heart rate, blood pressure, causes CNS stimulation and antidiuresis, and has hyperinsulinemic effects. By blocking central alpha2-receptors, yohimbine causes sympathetic outflow (norepinephrine) to be enhanced. Peripheral alpha2-receptors are also found in the cardiovascular system, genitourinary system, GI tract, in platelets, and adipose tissue.
Uses/Indications - Yohimbine is indicated to reverse the effects of xyalzine in dogs, but it is being used clinically in several other species as well. Yohimbine may be efficacious in reversing some of the toxic effects associated with other agents as well (e.g., amitraz), but additional research must be performed before additional recommendations for its use can be made.
Pharmacokinetics - The pharmacokinetics of this drug have been reported in steers, dogs, and horses (Jernigan et al. 1988). The apparent volume of distribution (steady-state) is approximately 5 L/kg in steers, 2 - 5 L/kg in horses, and 4.5 L/kg in dogs. The total body clearance is approximately 70 ml/min/kg in steers, 35 ml/min/kg in horses, and 30 ml/min/kg in dogs. The half-life of the drug is approximately 0.5 - 1 hours in steers, 0.5 - 1.5 hours in horses, and 1.5 - 2 hours in dogs.
Yohimbine is believed to penetrate the CNS quite readily and when used to reverse the effects of xylazine, onset of action generally occurs within 3 minutes. The metabolic fate of the drug is not known.
Contraindications/Precautions/Reproductive Safety - Yohimbine is contraindicated in patients hypersensitive to it. In humans, yohimbine is contraindicated in patients with renal disease. Yohimbine should be used cautiously in patients with seizure disorders. When used to reverse the effects xyalzine, normal pain perception may result.
Safe use of yohimbine in pregnant animals has not been established.
Adverse Effects/Warnings - Yohimbine may cause transient apprehension or CNS excitement, muscle tremors, salivation, increased respiratory rates, and hyperemic mucous membranes. Adverse effects appear to be more probable in small animals than in large animals.
Overdosage/Acute Toxicity - Dogs receiving 0.55 mg/kg (5 times recommended dose) exhibited symptoms of transient seizures and muscle tremors.
Drug Interactions - Little information is available, use with caution with other alpha2-adrenergic antagonists or other drugs that can cause CNS stimulation. In humans, yohimbine is recommended not to be used with antidepressants or other mood-altering agents.
For xylazine reversal:
a) 0.075 mg/kg IV (Gross and Tranquilli 1989)
For xylazine reversal:
a) 0.125 mg/kg (Cheeran et.al. 2002).
b) 0.05mg/kg yohimbine (route not specified) was effective in reversing ketamine-xylazine in 6 adult Asian elephants when administered 40 minutes after sedation (Sarma et.al. 2001).
c) Yohimbine (60-72 µg/kg IV) was used to reverse xylazine in 3 African elephant immobilizations (Ramsey, 2000).
d) Yohimbine is given at 0.5 times the xylazine dose (Kock et.al. 1993).
e) 50-250 mg in Asian elephants (Atapattu, 1991).
f) Yohimbine (0.13±0.03 mg/kg) given IV successfully reversed xylazine-ketamine anesthesia in 12 juvenile African elephants with a mean standing time of 2.4 ± 1.1 minutes (Jacobson et.al. 1985).
g) Yohimbine in combination with 4-aminopyridine reversed heavy xylazine sedation in an adult Asian elephant. See abstract below (Schmidt, 1983).
a) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K. 2002. Tranquilization and translocation of elephants. Journal of Indian Veterinary Association Kerala 7:(3):42-46
b)Sarma,K.K. and Pathak,S.C. 2001. Cardio vascular response to xylazine and Hellabrunn mixture with Yohimbine as reversal agent in Asian elephants. Indian Veterinary Journal 78:(5):400-492 Summary: Xylazine (0.1 mg/kg body weight) produced highly significant bradycardia and hypotension in recumbent Asian elephants, with a peak depression observed at the 30th minute for heart rate and 30th minute in the mean arterial pressure (MAP). Ketamine (1.25 : 1 ratio with xylazine) mildly marginalised the bradycardia, but remarkably improved the MAP. Yohimbine, used to reverse the sedation produced by xylazine did not appear to influence these parameters to any appreciable levels.
c) Ramsay,E. 2000. Standing sedation and tranquilization in captive African elephants (Loxodonta africana). Proc. Am. Assoc. Zoo Vet. Pages: 111-114
d) Kock,R.A., Morkel,P., and Kock,M.D., 1993. Current immobilization procedures used in elephants. In: Fowler,M.E. (Editor), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA pp. 436-441
e) Atapattu,N. 1991. Antagonism of xylazine induced sedation and immobilization in wild elephant (Elephas maximus maximus). International Seminar on Veterinary Medicine in Wild and Captive Animals, Nov. 8-10, Bangalore, India. Pages: 20 Abstract: Xylazine HCL has been the drug of choice for sedation of elephants. Sedated animals recover on its own after few hours. But there had been number of deaths in immobilized elephants after Xylazine induced sedation. Yohimbine HCL was tried on 10 wild elephants to antagonize Xylazine induced sedation. An initial dose of 50 mg of Yohimbine HCL was administered intravenously followed by a singular dose intramuscularly, similar doses were repeated in half an hour intervals. All the elephants recovered from Xylazine induced sedation after the treatment of Yohimbine HCL. The dose of Yohimbine HCL varied from 50 mg to 250 mg to complete recovery. The recommended dose of 0.13mg/kg had no significance on the body weight. The physical state of the animals, the dose of Xylazine HCL administered and other stress factors were more significant in deciding the dose of YohimbineHCL. All these animals were monitored for a period of one month and found their behaviour is recumbent laterally within 17 minutes and 2 remained standing, under deep sedation. Seven of the 8 elephants were given yohimbine (0.13 +/- 0.03 mg/kg) IV; all were ambulatory in 2 minutes. Results indicated that yohimbine may be useful in controlling duration of xylazine-ketamine sedation and immobilization in juvenile African elephants.
g) Schmidt,M.J. 1983. Antagonism of xylazine sedation by yohimbine and 4-aminopyridine in an adult Asian elephant (Elephas maximus). Journal of Zoo Animal Medicine 14:94-97 Summary: Heavy xylazine sedation was successfully antagonized by intravenous injection of yohimbine and 4-aminopyridine (4-AP) in an adult female Asian elephant (Elephas maximus) prior to euthanasia. A total xylazine dose of 1,200 mg intramuscularly plus 600 mg intravenously (approximately 0.33 mg/kg body weight) was given resulting in heavy sedation. After 50 minutes of deep recumbent sedation, 425 mg yohimbine and 1,000 mg of 4-AP were administered intravenously. Xylazine sedation was antagonized and the elephant was up and walking around within 5 minutes of antagonist administration. The elephant remained standing for other 3 hours; at which point euthanasia was performed.
Lance,W.R. 1991. New pharmaceutical tools for the 1990's. Proceedings of the American Association of Zoo Veterinarians 354-359
Monitoring Parameters -
1) CNS status (arousal level, etc.)
2) Cardiac rate; rhythm (if indicated), blood pressure (if indicated and practical)
3) Respiratory rate
Client Information - This agent should be used with direct professional supervision only.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Yohimbine Sterile Solution for Injection 2 mg/ml in 20 ml vials Yobine® (Lloyd); (Rx) Approved for use in dogs.
Yohimbine HCl Sterile Solution for Injection 5 mg/ml in 20 ml vials; Antagonil® (Wildlife Labs); (Rx) Approved for use in deer.
Oral 5.4 mg tablets are available, but would unlikely to be of veterinary
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