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

• The effects of alpha 2-agonist medetomidine (3 micrograms/kg) on the task performance were assessed in relation to individual variation in monoamine metabolism [6].
• The effect of systemic (intravenous) medetomidine, an alpha-2 adrenoceptor agonist, on pain thresholds was studied in healthy human subjects (n = 6) [7].
• 2. EEDQ administration also resulted in the loss of the sedative effect of the alpha 2-adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity [3].
• 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 [8].
• Effects of medetomidine, a selective alpha 2-agonist, on position discrimination and reversal learning in aged rats [9].

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

• Atipamezole clearly reversed the anaesthesia and bradycardia induced by medetomidine and ketamine [13].
• CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that equipotent low doses of medetomidine and xylazine induce comparable levels of ataxia and sedation and similar cardiopulmonary changes in adult horses [14].
• The isoflurane-sparing effect of the alpha 2-adrenergic agonist medetomidine (30 micrograms/kg of body weight, IV) was tested in 7 dogs, using a blinded, randomized-block study design [15].
• The combination of medetomidine with fentanyl was unsuitable for obtaining surgical anaesthesia in spontaneously breathing animals owing to the severity of the respiratory depression at dosages needed for general anaesthesia [16].
• Effects of preemptive atropine administration on incidence of medetomidine-induced bradycardia in dogs [17].

Biological context of Medetomidine

• Medetomidine-induced alterations of intraocular pressure and contraction of the nictitating membrane [18].
• 2. A 60 min i.v. infusion of medetomidine (0.2 or 0.6 microgram kg-1 min-1) decreased heart rate dose-dependently in both strains [19].
• Medetomidine infusion (0.6 microgram kg-1 min-1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR [19].
• 6. The specific uptake of [3H]-noradrenaline into cortical synaptosomes was inhibited by medetomidine and desmethylimipramine with IC50 values of approximately 7 microM and 8 microM respectively [20].
• We investigated changes in cardiac output and organ blood flow induced by medetomidine in sheep and determined changes in cardiac output and organ blood flow after reversal of medetomidine-induced sedation by atipamezole [21].

Anatomical context of Medetomidine

• Dissociation of the alpha 2-adrenergic antinociception from sedation following microinjection of medetomidine into the locus coeruleus in rats [22].
• In organ bath experiments, medetomidine reduced electrically evoked contractions of segments of the ileum from wild type but not alpha(2A)-knockout mice [23].
• The alpha 2-adrenergic agonist medetomidine produces systemic hemodynamic effects that are mediated by both peripheral and central nervous system actions [24].
• For comparison, medetomidine was microinjected into the cerebellum or the periaqueductal gray (PAG) [25].
• The current investigation was designed to characterize coronary and systemic hemodynamic effects of the D- and L-stereoisomers of medetomidine in conscious, chronically instrumented dogs with and without autonomic nervous system blockade [24].

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

• These results demonstrate that longitudinal fMRI studies can be performed safely under sedation with medetomidine to study functional recovery processes upon therapeutical treatment [12].
• Hypolocomotion (/sedation) was obtained at a lower medetomidine dose (1 microgram/cannula) than antinociception (3-10 micrograms/cannula) [22].
• Pain threshold to electric stimulation of the tooth pulp and cutaneous heat pain threshold were uninfluenced by medetomidine [7].
• Medetomidine, injected intraperitoneally, slowed gastrointestinal transit in wild type but not alpha(2A)-knockout mice [23].
• Medetomidine produced a dose-dependent (cumulative doses: 25 and 50 micrograms) sedative effect evaluated by visual analog scale [7].

References