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Chemical Compound Review

Precedex     4-[1-(2,3- dimethylphenyl)ethyl]-3H- imidazole

Synonyms: Medetomidina, Medetomidine, Medetomidinum, MPV-785, CHEMBL77921, ...
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Disease relevance of Medetomidine

  • The cardiovascular effects of clonidine and of two other imidazolic compounds (detomidine and medetomidine) are likely to be related to their alpha 2 adrenoceptor agonist properties since hypotension and bradycardia were completely antagonized by idazoxan [1].
  • After the development of mechanical hyperalgesia in the neuropathic limb, the responses of medial bulboreticular neurons to noxious skin stimulation were determined, and the attenuation of the responses was attempted by administering systemically medetomidine, a highly specific alpha 2-adrenoceptor agonist [2].
  • 3. EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg-1, i.p.). Medetomidine-induced hypothermia returned to control values by 12 days post EEDQ administration [3].
  • The effects of medetomidine were blocked by systemic atipamezole (75 micrograms/kg, i.v.), which, when injected alone, had no effect on the number of Fos-LI neurons or the peripheral edema [4].
  • Neither the behavioral effect of pertussis holotoxin in the holeboard nor its effects on reversing medetomidine hypolocomotion or ethanol-induced ataxia were seen following administration of the binding oligomer of pertussis toxin which binds to the cell membrane but does not possess the enzymatically active subunit [5].

Psychiatry related information on Medetomidine


High impact information on Medetomidine

  • BACKGROUND: The effects of selective alpha-agonist medetomidine and alpha 2-antagonist atipamezole on gastrointestinal motility were studied [10].
  • RESULTS: Subcutaneous medetomidine, 0.01-0.1 mg/kg, was found to delay small intestinal transit but not gastric emptying, with a maximal effect seen at 0.03 mg/kg [10].
  • In behavioral studies alpha-2-adrenoceptor agonists, including medetomidine, produce antinociception following systemic administration or local application to the spinal cord [11].
  • Paradoxically, the response of immediate early genes in the medial thalamic neurons is only slightly, influenced by antinociceptive doses of medetomidine [11].
  • A robust and reproducible, significant BOLD signal increase was observed upon forepaw stimulation in the contralateral primary somatosensory cortex in two consecutive medetomidine sessions in all rats, which was similar to the BOLD signal increase observed in the same animals under alpha-chloralose during a third independent session [12].

Chemical compound and disease context of Medetomidine


Biological context of Medetomidine


Anatomical context of Medetomidine


Associations of Medetomidine with other chemical compounds

  • Ketamine as a probe for medetomidine stereoisomer inhibition of human liver microsomal drug metabolism [26].
  • Dexmedetomidine (the D-stereoisomer of medetomidine), a highly selective alpha 2-adrenoceptor agonist, has been demonstrated to produce analgesia and sedation and attenuate hemodynamic responses to emergence from inhalational anesthetics, which suggests a potential use for this drug as a premedicant for general anesthesia [27].
  • When administered into the RVM, medetomidine produced a dose-dependent (1-30 micrograms) antinociception in the tail-flick and hot-plate tests, which antinociceptive effect was completely reversed by atipamezole (1 mg/kg, s.c.). Also clonidine produced a dose-dependent (3-30 micrograms) antinociception following microinjection into the RVM [25].
  • In terms of a reduction of the amount of fentanyl needed to produce a deep surgical analgesia (tail-withdrawal reaction latency > or = 10 s) over more than 2 h, the relative order of potency of the alpha 2 agonists tested was: medetomidine > dexmedetomidine > xylazine > clonidine > detomidine [28].
  • Noradrenaline or medetomidine were microinjected into the grey matter of the spinal cord, near microprobe insertion sites, at depths of 2.5, 2.0, 1.5 and 1.0 mm below the spinal cord surface with volumes of approximately 0.125 microliters and a concentration of 10(-3) M [29].

Gene context of Medetomidine

  • The effects of medetomidine did not differ in NMRI, wildtype, alpha2BKO and alpha2CKO mice but were greatly reduced in alpha2A/DKO brain preparations and to a lesser extent in alpha2A/DKO atria and vasa deferentia [30].
  • The effect of medetomidine, an alpha 2-adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar-Kyoto rats [19].
  • The pK(d) values of the five antagonists against medetomidine in alpha(2AC)KO atria and vasa deferentia correlated with pK(d) values at prototypical alpha(2B) radioligand binding sites but not at alpha(2A) or alpha(2C) binding sites [31].
  • Infusion of medetomidine did not have a significant effect on basal PRL levels; however, a trend toward a significant elevation was observed for the highest dose [32].
  • Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine [33].

Analytical, diagnostic and therapeutic context of Medetomidine


  1. Changes in serotonin metabolism in the rat raphe magnus and cardiovascular modifications following systemic administration of clonidine and other central alpha 2-agonists: an in vivo voltammetry study. Aslanian, V., Renaud, B. Neuropharmacology (1989) [Pubmed]
  2. Influence of an experimental peripheral mononeuropathy on the responses of medial bulboreticular neurons to noxious skin stimulation and the modulation of the responses by an alpha 2-adrenoceptor agonist in the rat. Luukko, M., Pertovaara, A. Exp. Neurol. (1993) [Pubmed]
  3. Covariation of alpha 2-adrenoceptor density and function following irreversible antagonism with EEDQ. Durcan, M.J., Morgan, P.F., Van Etten, M.L., Linnoila, M. Br. J. Pharmacol. (1994) [Pubmed]
  4. To what extent do spinal interactions between an alpha-2 adrenoceptor agonist and a mu opioid agonist influence noxiously evoked c-Fos expression in the rat? A pharmacological study. Honoré, P., Chapman, V., Buritova, J., Besson, J.M. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  5. Interactions of intracerebroventricular pertussis toxin treatment with the ataxic and hypothermic effects of ethanol. Durcan, M.J., Lister, R.G., Morgan, P.F., Linnoila, M. Naunyn Schmiedebergs Arch. Pharmacol. (1991) [Pubmed]
  6. Effect of sex and age on brain monoamines and spatial learning in rats. Tanila, H., Taira, T., Piepponen, T.P., Honkanen, A. Neurobiol. Aging (1994) [Pubmed]
  7. Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans. Kauppila, T., Kemppainen, P., Tanila, H., Pertovaara, A. Anesthesiology (1991) [Pubmed]
  8. The effects of alpha-2 agonist, medetomidine and its antagonist, atipamezole on reaction and movement times in a visual choice reaction time task in monkeys. Rämä, P., Linnankoski, I., Carlson, S. Brain Res. Bull. (1997) [Pubmed]
  9. Effects of medetomidine, a selective alpha 2-agonist, on position discrimination and reversal learning in aged rats. Tanila, H. Pharmacol. Biochem. Behav. (1993) [Pubmed]
  10. Inhibition of intestinal motility and reversal of postlaparotomy ileus by selective alpha 2-adrenergic drugs in the rat. Tanila, H., Kauppila, T., Taira, T. Gastroenterology (1993) [Pubmed]
  11. Antinociception induced by alpha-2-adrenoceptor agonists, with special emphasis on medetomidine studies. Pertovaara, A. Prog. Neurobiol. (1993) [Pubmed]
  12. A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat. Weber, R., Ramos-Cabrer, P., Wiedermann, D., van Camp, N., Hoehn, M. Neuroimage (2006) [Pubmed]
  13. Antagonistic activities of atipamezole, 4-aminopyridine and yohimbine against medetomidine/ketamine-induced anaesthesia in cats. Verstegen, J., Fargetton, X., Zanker, S., Donnay, I., Ectors, F. Vet. Rec. (1991) [Pubmed]
  14. Cardiopulmonary and sedative effects of intravenous administration of low doses of medetomidine and xylazine to adult horses. Bueno, A.C., Cornick-Seahorn, J., Seahorn, T.L., Hosgood, G., Moore, R.M. Am. J. Vet. Res. (1999) [Pubmed]
  15. Reduction of isoflurane anesthetic requirement by medetomidine and its restoration by atipamezole in dogs. Ewing, K.K., Mohammed, H.O., Scarlett, J.M., Short, C.E. Am. J. Vet. Res. (1993) [Pubmed]
  16. Medetomidine as a premedicant for ketamine, propofol or fentanyl anaesthesia in dogs. Hellebrekers, L.J., Sap, R. Vet. Rec. (1997) [Pubmed]
  17. Effects of preemptive atropine administration on incidence of medetomidine-induced bradycardia in dogs. Ko, J.C., Fox, S.M., Mandsager, R.E. J. Am. Vet. Med. Assoc. (2001) [Pubmed]
  18. Medetomidine-induced alterations of intraocular pressure and contraction of the nictitating membrane. Potter, D.E., Ogidigben, M.J. Invest. Ophthalmol. Vis. Sci. (1991) [Pubmed]
  19. The effect of medetomidine, an alpha 2-adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar-Kyoto rats. Ruskoaho, H., Leppäluoto, J. Br. J. Pharmacol. (1989) [Pubmed]
  20. Contrasting effects of the imidazol(in)e alpha 2-adrenoceptor agonists, medetomidine, clonidine and UK 14,304 on extraneuronal levels of noradrenaline in the rat frontal cortex: evaluation using in vivo microdialysis and synaptosomal uptake studies. Dalley, J.W., Stanford, S.C. Br. J. Pharmacol. (1995) [Pubmed]
  21. The effect of alpha(2) agonist-induced sedation and its reversal with an alpha(2) antagonist on organ blood flow in sheep. Talke, P.O., Traber, D.L., Richardson, C.A., Harper, D.D., Traber, L.D. Anesth. Analg. (2000) [Pubmed]
  22. Dissociation of the alpha 2-adrenergic antinociception from sedation following microinjection of medetomidine into the locus coeruleus in rats. Pertovaara, A., Hämäläinen, M.M., Kauppila, T., Mecke, E., Carlson, S. Pain (1994) [Pubmed]
  23. Alpha 2-adrenoceptors in the enteric nervous system: a study in alpha 2A-adrenoceptor-deficient mice. Scheibner, J., Trendelenburg, A.U., Hein, L., Starke, K., Blandizzi, C. Br. J. Pharmacol. (2002) [Pubmed]
  24. The effects of the stereoisomers of the alpha 2-adrenergic agonist medetomidine on systemic and coronary hemodynamics in conscious dogs. Schmeling, W.T., Kampine, J.P., Roerig, D.L., Warltier, D.C. Anesthesiology (1991) [Pubmed]
  25. The rostroventromedial medulla is not involved in alpha 2-adrenoceptor-mediated antinociception in the rat. Hämäläinen, M.M., Pertovaara, A. Neuropharmacology (1993) [Pubmed]
  26. Ketamine as a probe for medetomidine stereoisomer inhibition of human liver microsomal drug metabolism. Kharasch, E.D., Herrmann, S., Labroo, R. Anesthesiology (1992) [Pubmed]
  27. Premedication with oral dexmedetomidine alters hemodynamic actions of intravenous anesthetic agents in chronically instrumented dogs. Proctor, L.T., Schmeling, W.T., Warltier, D.C. Anesthesiology (1992) [Pubmed]
  28. Potentiation of the analgesic properties of fentanyl-like opioids with alpha 2-adrenoceptor agonists in rats. Meert, T.F., De Kock, M. Anesthesiology (1994) [Pubmed]
  29. Lack of effect of microinjection of noradrenaline or medetomidine on stimulus-evoked release of substance P in the spinal cord of the cat: a study with antibody microprobes. Lang, C.W., Hope, P.J., Grubb, B.D., Duggan, A.W. Br. J. Pharmacol. (1994) [Pubmed]
  30. A study of presynaptic alpha2-autoreceptors in alpha2A/D-, alpha2B- and alpha2C-adrenoceptor-deficient mice. Trendelenburg, A.U., Klebroff, W., Hein, L., Starke, K. Naunyn Schmiedebergs Arch. Pharmacol. (2001) [Pubmed]
  31. All three alpha2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons. Trendelenburg, A.U., Philipp, M., Meyer, A., Klebroff, W., Hein, L., Starke, K. Naunyn Schmiedebergs Arch. Pharmacol. (2003) [Pubmed]
  32. Infusion of alpha-2-adrenergic agents into the paraventricular and arcuate nuclei of the hypothalamus in the Siberian hamster: opposing effects on basal prolactin. Dodge, J.C., Badura, L.L. Neuroendocrinology (2002) [Pubmed]
  33. Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative. MacDonald, E., Scheinin, H., Scheinin, M. Eur. J. Pharmacol. (1988) [Pubmed]
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