Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats



      To evaluate the effects of medetomidine and its antagonism with atipamezole in goats.

      Study design

      Prospective randomized crossover study with 1 week between treatments.


      Six healthy 3-year-old neutered goats (three male and three female) weighing 39.1–90.9 kg (60.0 ± 18 kg, mean ± SD).


      Goats were given medetomidine (20 μg kg−1, IV) followed, 25 minutes later, by either atipamezole (100 μg kg−1, IV) or saline. Heart and respiratory rate, rectal temperature, indirect blood pressure, and mechanical threshold were measured, and sedation and posture were scored and blood samples obtained to measure epinephrine, norepinephrine, free fatty acids, glucose, and cortisol concentrations at baseline (immediately before medetomidine), 5 and 25 minutes after medetomidine administration, and at 5, 30, 60, and 120 minutes after the administration of antagonist or saline. Parametric and nonparametric tests were used to evaluate data; p < 0.05 was considered significant.


      Medetomidine decreased body temperature, heart rate, and respiratory rate and increased mean arterial blood pressure, cortisol, and glucose. Recumbency occurred 89 ± 50 seconds after medetomidine administration. All goats were standing 86 ± 24 seconds after atipamezole administration whereas all goats administered saline were sedate and recumbent at 2 hours. Tolerance to compression of the withers and metacarpus increased with medetomidine. From 5 to 120 minutes after saline or atipamezole administration, there were differences in body temperature, glucose, and cortisol but none in heart rate or blood pressure. Three of the six goats receiving saline developed bloat; five of six urinated. After atipamezole, four of six goats developed piloerection and all goats were agitated and vocalized.


      At the doses used, atipamezole antagonized the effects of medetomidine on recumbency, sedation, mechanical threshold, and the increase in glucose. Atipamezole increased the rate of return of cortisol toward baseline, and prevented further decline in rectal body temperature.

      Clinical relevance

      Atipamezole may be used to antagonize some, but not all effects of medetomidine.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Veterinary Anaesthesia and Analgesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Aantaa R
        Alpha-2 adrenoceptor agonists in human anaesthesiology and intensive care.
        in: Proceedings of the Seventh World Congress of Veterinary Anaesthesia. Berne, Switzerland2000: 13-16
        • Arnemo JM
        • Soli NE
        Chemical capture of free-ranging cattle: immobilization with xylazine or medetomidine, and reversal with atipamezole.
        Vet Res Commun. 1993; 17: 469-477
        • Benson GJ
        • Grubb TL
        • Neff-Davis C
        • et al.
        Perioperative stress response in the dog: effect of pre-emptive administration of medetomidine.
        Vet Surg. 2000; 29: 85-91
        • Bryant CE
        • Clarke KW
        • Thompson J
        Cardiopulmonary effects of medetomidine in sheep and ponies.
        Res Vet Sci. 1996; 60: 267-271
        • Bryant CE
        • Thompson J
        • Clarke KW
        Characterization of the cardiovascular pharmacology of medetomidine in the horse and sheep.
        Res Vet Sci. 1998; 65: 149-154
        • Carroll GL
        • Matthews NS
        • Hartsfield SM
        • et al.
        The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies.
        Vet Surg. 1997; 26: 69-77
        • Carroll GL
        • Hartsfield SM
        • Champney TH
        • et al.
        Stress-related hormonal and metabolic responses to restraint, with and without butorphanol administration, in pre-conditioned goats.
        Lab Anim Sci. 1998; 48: 387-390
        • Carroll GL
        • Boothe DM
        • Hartsfield SM
        • et al.
        Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.
        J Am Vet Med Assoc. 2001; 219: 1263-1267
        • Celly CS
        • McDonell WN
        • Young SS
        • et al.
        The comparative hypoxaemic effect of four α adrenoceptor agonists (xylazine, romifidne, detomidine and medetomidine) in sheep.
        J Vet Pharmacol Ther. 1997; 20: 446-471
        • Celly CS
        • McDonell WN
        • Black WD
        Cardiopulmonary effects of the α2-adrenoceptor agonists medetomidine and ST-91 in anesthetized sheep.
        J Pharmacol Exp Ther. 1999; 289: 712-720
        • Champney TH
        • Steger RW
        • Christie DS
        • et al.
        Alterations in components of the melatonin synthetic pathway by acute insulin stress in the rat and Syrian hamster.
        Brain Res. 1985; 338: 25-32
        • Dantzer R
        Assessing pain by studying neuroendocrine responses.
        in: Duncan IJH Maloney V Assessing Pain in Farm Animals. Commission of European Communities, Luxembourg1986: 39-48
        • DeMoor A
        • Desmet P
        Effects of Rompun on acid-base equilibrium and arterial O2 pressure in cattle.
        Vet Med Rev. 1971; 2/3: 163-169
        • Dyck JB
        • Maze M
        • Haak C
        • et al.
        The pharmacokinetics and hemodynamic effects of intravenous and intramuscular dexmedetomidine hydrochloride in adult human volunteers.
        Anesthesiology. 1993; 78: 813-820
        • Eisenach JC
        Intravenous clonidine produces hypoxemia by a peripheral alpha2 adrenergic mechanism.
        J Pharmacol Exp Ther. 1988; 244: 247-252
        • Eissa HM
        • Ahmed AS
        • Serur BH
        • et al.
        Influence of general anesthesia (thiopental sodium) on progesterone and cortisol levels in pregnant goat serum.
        Arch Exp Vet Med. 1990; 44: 621-625
        • Esler M
        • Jennings G
        • Korner P
        • et al.
        Measurement of total and organ-specific norepinephrine kinetics in humans.
        Am J Physiol. 1984; 247: E21-E28
        • Guyton AC
        Textbook of Medical Physiology. 8th edn. Saunders, Philadelphia, PA1991: 812
        • Hall LW
        • Clarke KW
        Principles of Sedation, Analgesia and Premedication. Veterinary Anaesthesia. 9th edn. Balliere Tindall, London, England1991: 60
        • Hargraves KM
        Neuroendocrine markers of stress.
        Anesth Prog. 1990; 37: 99-105
        • Hartsfield SM
        • Carroll GL
        • Martinez EA
        • et al.
        Antagonism of xylazine or medetomidine sedation in goats with yohimbine, tolazoline, atipamezole, and saline.
        Vet Surg. 1999; 28: 133
        • Hsu WH
        Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep.
        J Am Vet Med Assoc. 1987; 190: 423-426
        • Kallio A
        • Koulu M
        • Scheinin H
        • et al.
        Acute effects of medetomidine, a selective α2-adrenoceptor agonist, on anterior pituitary hormone and cortisol secretion in man.
        Acta Endocrinol. 1988; 119: 11-15
        • Kallio A
        • Scheinin M
        • Koulu M
        • et al.
        Effects of dexmedetomidine, a selective α2-adrenoceptor agonist, on hemodynamic control mechanisms.
        Clin Pharmacol Ther. 1989; 46: 33-46
        • Kallio A
        • Salonen M
        • Forssell H
        • et al.
        Medetomidine premedication in dental surgery – a double-blind cross-over study with a new α2-adrenoceptor agonist.
        Acta Anaesthesiol Scand. 1990; 34: 171-175
        • Karns PA
        • Kamerling SG
        • Bagwell CA
        Quantification of equine hoof lameness using an electronic hoof tester.
        in: Proceedings of the 6th International Conference of Racing Analysts and Veterinarians. Hong Kong, China1988: 325-329
        • Kastner SBR
        • von Rechenberg B
        • Keller K
        • et al.
        Comparison of medetomidine and dexmedetomidine as premedication in isoflurane anaesthesia for orthopaedic surgery in domestic sheep.
        J Vet Med. 2001; 48: 231-241
        • Kastner SBR
        • Wapf P
        • Feige K
        • et al.
        Pharmacokinetics and sedative effects of intramuscular medetomidine in sheep.
        J Vet Pharmacol Ther. 2003; 26: 271-276
        • Kilgour R
        • DeLangen H
        Stress in sheep resulting from management practices.
        Proc N Z Soc Anim Prod. 1970; 30: 65-76
        • Kitzman JV
        • Booth NH
        • Hatch RC
        • et al.
        Antagonism of xylazine sedation by 4-aminopyridine and yohimbine in cattle.
        Am J Vet Res. 1982; 43: 2165-2169
        • Ko JCH
        • McGrath CJ
        Effects of atipamezole and yohimbine on medetomidine-induced central nervous system depression and cardiorespiratory changes in lambs.
        Am J Vet Res. 1995; 56: 629-632
        • McCutcheon SN
        • Bauman DE
        Effect of chronic growth hormone treatment on responses to epinephrine and thyrotropin–releasing hormone in lactating cows.
        J Dairy Sci. 1986; 69: 44-51
        • Mohammad FK
        • Zangana IK
        • Abdul-Latif AR
        Medetomidine sedation in sheep.
        J Vet Med. 1993; 40: 328-331
        • Mohammad FK
        • Zangana IK
        • Abdul-Latif AR
        Reversal of medetomidine sedation in sheep by atipamezole and yohimbine.
        Vet Human Toxicol. 1995; 37: 97-99
        • Mpanduji DG
        • Bittegeko SBP
        • Mgasa MN
        • et al.
        Analgesic, behavioral and cardiopulmonary effects of epidurally injected medetomidine (Domitor®) in goats.
        J Vet Med A. 2000; 47: 65-72
        • Nolan AM
        • Callingham BA
        Effects of aspirin on xylazine-induced hypoxaemia in sheep.
        Res Vet Sci. 1990; 48: 388-398
        • Opie LH
        Effect of free fatty acids on the heart.
        Nature. 1970; 227: 1055-1056
        • Pearson RA
        • Mellor DJ
        Some physiological changes in pregnant sheep and goats before, during and after surgical insertion of uterine catheters.
        Res Vet Sci. 1975; 19: 102-104
        • Raekallio M
        • Vainio O
        • Scheinin M
        • et al.
        Detomidine reduces the plasma catecholamine but not cortisol concentrations in horses.
        J Vet Med Ser A. 1991; 38: 153-156
        • Raekallio M
        • Leino A
        • Vainio O
        • et al.
        Sympatho-adrenal activity and the clinical sedative effect of detomidine in horses.
        Equine Pharm Suppl. 1992; 11: 66-68
        • Raekallio M
        • Hackzell M
        • Eriksson L
        Influence of medetomidine on acid-base balance and urine excretion in goats.
        Acta Vet Scand. 1994; 35: 283-288
        • Ranheim B
        • Arnemo JM
        • Ryeng KA
        • et al.
        A pharmacokinetic study including some relevant clinical effects of medetomidine and atipamezole in lactating dairy cows.
        J Vet Pharmacol Ther. 1999; 22: 368-373
        • Ranheim B
        • Arnemo JM
        • Stuen S
        • et al.
        Medetomidine and atipamezole in sheep: disposition and clinical effects.
        J Vet Pharmacol Ther. 2000; 23: 401-404
        • Ranheim B
        • Horsberg TE
        • Soli NE
        • et al.
        The effects of medetomidine and its reversal with atipamezole on plasma glucose, cortisol and noradrenaline in cattle and sheep.
        J Vet Pharmacol Ther. 2000; 23: 379-387
        • Read MR
        • Duke T
        • Toews AR
        Suspected tolazoline toxicosis in a llama.
        J Am Vet Med Assoc. 2000; 216: 227-229
        • Reibold TW
        • Geiser DR
        • Goble DO
        Anesthetic agents and ancillary drugs.
        in: Reibold TW Geiser DR Goble DO Large Animal Anesthesia. 2nd edn. Iowa State University Press, Ames, IA, USA1995: 11-64
        • Sanhouri AA
        • Jones RS
        • Dobson H
        Plasma concentrations of cortisol, testosterone, glucose, and blood gases in male goats during anaesthesia with pentobarbitone sodium.
        Br Vet J. 1990; 146: 36-42
        • Sanhouri AA
        • Jones RS
        • Dobson H
        Pentobarbitone inhibits the stress response to transport in male goats.
        Br Vet J. 1991; 147: 42-48
        • Sanhouri AA
        • Jones RS
        • Dobson H
        Effects of xylazine on the stress response to transport in male goats.
        Br Vet J. 1992; 148: 119-148
        • Savola JM
        Cardiovascular actions of medetomidine and their reversal by atipamezole.
        Acta Vet Scand (Suppl). 1989; 85: 39-47
        • Scheinin H
        • Kallio A
        • Koulu M
        • et al.
        Pharmacological effects of medetomidine in humans.
        Acta Vet Scand. 1989; 85: 145-147
        • Scheinin H
        • Aantaa R
        • Anttila M
        • et al.
        Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole. A pharmacologic and kinetic study in healthy volunteers.
        Anesthesiology. 1998; 89: 574-584
        • Taylor PM
        Equine stress response to anaesthesia.
        Br J Anaesth. 1989; 63: 702-709
        • Taylor PM
        The stress response to anaesthesia in ponies: barbiturate anaesthesia.
        Equine Vet J. 1990; 22: 307-312
        • Tranquilli W
        Anesthetic reversal agents.
        in: American College of Veterinary Surgeons 1993 Veterinary Symposium. 1993: 419-421 (San Francisco, CA, USA)
        • Waldridge BM
        • Lin H-C
        • DeGraves FJ
        • et al.
        Sedative effects of medetomidine and its reversal by atipamezole in llamas.
        J Am Vet Med Assoc. 1997; 211: 1562-1565
        • Waterman AE
        • Nolan A
        • Livingston A
        Influence if idazoxan on the respiratory blood gas changes induced by alpha2-adrenoceptor agonist drugs in conscious sheep.
        Vet Rec. 1987; 121: 105-107
        • Young PL
        The effect of xylazine on body temperature of cattle.
        Aust Vet J. 1979; 55: 442-443