Disease relevance of MPV 1440

• Dexmedetomidine is a highly specific alpha2-adrenergic agonist, which is used clinically as an anesthetic adjuvant and in animal experiments has a neuroprotective effect during ischemia [1].
• Neither dexmedetomidine, an alpha-2 adrenergic agonist, nor isoproterenol, a beta adrenergic agonist, caused situs inversus [2].
• Dexmedetomidine-induced ocular hypotension in rabbits with normal or elevated intraocular pressures [3].
• In rats, dexmedetomidine creates bradycardia, sedation/hypnosis, sympathoadrenal blocking effects, and blood pressure-increasing effects at plasma concentrations below 2.5 ng/ml [4].
• These data show that addition of the alpha 2-agonist dexmedetomidine will not worsen the cardiovascular and respiratory depression associated with high-dose opiates in the spontaneously ventilating rat [5].

Psychiatry related information on MPV 1440

• The effects of dexmedetomidine, a subtype-nonselective alpha 2-AR agonist, on monoamine turnover in brain and on locomotor activity were similar in mice with targeted inactivation of the alpha 2C-AR gene and in their controls, but the hypothermic effect of the alpha 2-AR agonist was significantly attenuated by the receptor gene inactivation [6].
• The antinociceptive effect of dexmedetomidine was measured using the tail-flick latency response [7].
• In part 2, dexmedetomidine induced clear impairments of vigilance and psychomotor performance that were dose dependently reversed by atipamezole (P < 0.001) [8].
• OBJECTIVE: Dexmedetomidine (DEX) may provide a sedation level that enables sleep and communication, with less amnesia and pain medication requirements, during mechanical ventilation [9].
• RESULTS: Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam [10].

High impact information on MPV 1440

• Therefore, the alpha2A adrenoceptor subtype is responsible for the hypnotic response to dexmedetomidine in the locus coeruleus of the rat [11].
• Treatment of LLC-PK1-alpha(2B) with UK14304 or dexmedetomidine caused arachidonic acid (AA) release and ERK2 phosphorylation [12].
• Variables assessed included surgeon experience, patient demographics, comorbidities, operative time, Roux limb pathway, intraoperative steroid bolus, and use of dexmedetomidine [13].
• The current study showed that dexmedetomidine enhances glutamine disposal by oxidative metabolism in astrocytes [1].
• A trend toward an increase in the pulsatility index at the higher levels of dexmedetomidine suggests that the observed decrement in CBF velocity was due to an increase in cerebral vascular resistance [14].

Chemical compound and disease context of MPV 1440

• Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine [15].
• Propofol-induced dyskinesias controlled with dexmedetomidine during deep brain stimulation surgery [16].
• In contrast, dexmedetomidine does not suppress elevation in brain norepinephrine and glutamate concentration associated with cerebral ischemia [17].
• Intrathecal administration of atipamezole and pertussis toxin also blocked the antinociceptive effect of dexmedetomidine placed in the LC [7].
• Mechanism of antiarrhythmic effect of dexmedetomidine on epinephrine-induced arrhythmias [18].

Biological context of MPV 1440

• Pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine [19].
• Dexmedetomidine produced a predictable haemodynamic decline (dose-dependently decreased arterial blood pressure and heart rate) in postsurgical patients coinciding with reductions in plasma catecholamines [20].
• These results indicate that the selective alpha 2-adrenoceptor agonist, dexmedetomidine, is a potent and effective drug for decreasing intraocular pressure in rabbits [3].
• Dexmedetomidine blunts heart rate and the systemic sympathetic activation due to sweating, but it is less effective in blunting cardiac sympathetic responses to shivering [21].
• CONCLUSIONS: The results of this study are the first to characterize the lower end of the dose-response curve for vasoconstriction induced by dexmedetomidine [22].

Anatomical context of MPV 1440

• Serial measurements of middle cerebral artery blood flow velocity at four steady-state plasma concentrations of dexmedetomidine were made with a 2-MHz transcranial Doppler transducer via the temporal window [14].
• The consistent finding that these two alpha(2)-adrenoceptor agonists interact in a supra-additive manner provides strong evidence that dexmedetomidine and ST-91 produce antinociception by acting at different alpha(2)-adrenoceptor subtypes in the spinal cord [23].
• In the familiar environment, DEX significantly increased the mean firing rate of hippocampal interneurons, while ATI increased the mean firing rate of pyramidal cells [24].
• After unilateral topical administration, dexmedetomidine (0.5 mg/ml, 25 microliters) lowered intraocular pressure bilaterally in normal rabbits and in rabbits with intraocular pressure elevated after laser irradiation of the pigmented trabecular band of the anterior chamber angle [3].
• Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting [25].

Associations of MPV 1440 with other chemical compounds

• In both cell types, the alpha(2B)-AR is coupled to G protein, and its stimulation by dexmedetomidine, but not by UK-14304, provoked a significant inhibition of the accumulation of cAMP induced by forskolin or parathyroid hormone [26].
• Dexmedetomidine at 100 nM inhibited both AVP- and 8CPTcAMP-stimulated Pf [27].
• In the EEDQ experiments, the analgesic response to dexmedetomidine was restored to normal when 44% of the alpha 2 adrenoceptors in the spinal cord were available for agonist binding; comparatively more alpha 2 adrenoceptors (77%) were required for the analgesic response to clonidine to be restored [28].
• CONCLUSIONS: Dexmedetomidine reduced propofol requirements and improved hemodynamic stability during bispectral index-guided intensive care unit sedation [29].
• The effect of local introduction of the alpha2-adrenoceptor agonist dexmedetomidine (10-9-10-8 m) on noradrenaline and dopamine release was investigated in alpha2A-adrenoceptor knockout and control mice by using in vivo microdialysis [30].

Gene context of MPV 1440

• Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype [31].
• Addition of dexmedetomidine (10 microM), an alpha 2-adrenergic agonist, did not change the baseline release of either CGRP or SP, but significantly decreased the CAP-evoked release of both peptides [32].
• The administration of the alpha 2-agonist, dexmedetomidine, to HTM cells resulted in a 90% inhibition of forskolin-stimulated cAMP formation, a twofold stimulation of MAP kinase activity, and a threefold increase in the expression of PCNA [33].
• METHODS: The effects of dexmedetomidine on phospho-tyrosine FAK phosphorylation were studied first with or without various pharmacologic agents in normoxic conditions, and second in a model of pharmacologic preconditioning of slices subjected to 30 min of OGD followed by 1 h of reperfusion [34].
• CONCLUSIONS: The present data demonstrate that dexmedetomidine effectively prevents delayed neuronal death in CA3 area and in the dentate hilus in gerbil hippocampus when the management is started before the onset of ischemia and continued for 48 h after reperfusion [35].

Analytical, diagnostic and therapeutic context of MPV 1440

• Dexmedetomidine is a potentially useful tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in human beings and may have therapeutic applications in clinical conditions in which sedative and sympatholytic effects are considered beneficial, such as premedication for anesthesia and surgery [36].
• Single intramuscular doses of dexmedetomidine (0.5, 1.0, and 1.5 microgram/kg) and placebo were administered to six subjects in a single-blind, multiple crossover study [19].
• Dexmedetomidine decreases cerebral blood flow velocity in humans [14].
• Dexmedetomidine, a potent alpha-2 adrenergic agonist, was administered by computer-driven infusion pump to six male volunteers [14].
• This study was designed to determine the effects of dexmedetomidine on CBF velocity as measured by transcranial Doppler sonography in human volunteers [14].

References