Disease relevance of Mivazerol

• Mivazerol did not reduce the rate of calcium change during simulated ischemia [1].
• Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT) [2].
• Mivazerol decreased hypoxia and KCl1-evoked glutamate release by 50% and 75% (p < 0.01), respectively [1].
• CONCLUSION: The alpha2-adrenergic agonist, mivazerol, did not alter the rates of myocardial infarction or cardiac death in patients with known coronary heart disease undergoing noncardiac surgery [2].
• We studied the effects of mivazerol during periods of moderate coronary artery stenosis in anesthetized dogs [3].

High impact information on Mivazerol

• However, neither mivazerol nor clonidine, at doses up to 10 microM, had any significant effect on KCI-induced glutamate release in spinal cord, whereas mivazerol blocked completely the release of both amino acids in hippocampus and only the release of aspartate in spinal cord [4].
• 4. Basal NA levels in conscious animals were not affected by an intravenous infusion of equally radioactive solutions of either imidazoline (clonidine) or imidazole (mivazerol) alpha2-adrenoceptor agonists [5].
• The selective alpha 2-agonist mivazerol (1 microM) decreased NMDA receptor-mediated calcium changes in hippocampal CA1 neurons by 28% (p = 0.0079) [1].
• Mivazerol, 3-[1(H-imidazol-4-yl)methyl]-2-hydroxybenzamide hydrochloride, a new potential anti-ischemic drug designed by UCB S.A. Pharma Sector, has been studied in binding experiments on adrenergic, dopaminergic, serotoninergic, muscarinic and idazoxan binding sites [6].
• Mivazerol was also a potent competitor for [3H]RX 821002 binding to human platelet membranes (containing alpha 2A adrenoceptors) and rat kidney membranes (75% of the alpha 2 adrenoceptors of the alpha 2B subtype), indicating that this compound is not alpha 2 adrenoceptor subtype selective [6].

Chemical compound and disease context of Mivazerol

• With hypoxia and 3 mM glutamate, 1 microM mivazerol reduced early peak calcium changes in CA1 neurons by 57% (p = 0.0007) [1].
• Mivazerol, 3-[1(H-imidazol-4-yl)methyl]-2-hydroxybenzamide hydrochloride, is a selective alpha 2-adrenoceptor agonist designed for the prevention of myocardial infarction in perioperative patients [7].
• Bradycardia induced by mivazerol, a selective alpha 2-adrenoceptor agonist, is amplified during mild hypothermia in the pentobarbital-anesthetized rat [7].

Biological context of Mivazerol

• The intravenous (i.v.) infusion of mivazerol, a new selective alpha 2-adrenoceptor agonist, produced a significant decrease in heart rate but not in blood pressure in pentobarbital-anesthetized Sprague-Dawley rats [8].
• Mivazerol had no effect on myocardial oxygen extraction during the stenoses, and regional myocardial oxygen consumption was unchanged [3].
• Because unintended hypothermia occurs frequently during surgery, we were interested, in this study, to examine the relationship between body temperature and the bradycardic response induced by mivazerol [7].
• A specific alpha(2) agonist, mivazerol, known to be effective in reducing myocardial ischaemia when given intravenously immediately before an exercise tolerance test, produced a significant increase in exercise duration and time to the onset of angina when given orally over a two week period to 25 patients with stable angina [9].

Anatomical context of Mivazerol

• Mivazerol displaced the binding of the alpha 2 adrenoceptor antagonist [3H]RX 821002 to the alpha 2A adrenoceptors in human frontal cortex membranes with an apparent Ki value of 37 nM [6].
• Mivazerol reduced blood flow in nonischemic myocardium and in the ischemic epicardial layer, but blood flow was preserved in the ischemic midmyocardial and subendocardial layer [3].
• Neuroprotective effect of mivazerol, an alpha 2-agonist, after transient forebrain ischemia in rats [10].
• This action of mivazerol depends on a well documented centrally mediated reduction in sympathetic nerve activity, but a direct peripheral decrease in sympathetic neurotransmitter release induced by activation of prejunctional alpha 2-adrenoceptors located on sympathetic nerve endings could also contribute [11].
• Mivazerol may improve exercise performance by attenuating the effects of exercise-induced sympathetic nervous system activity on the ischemic myocardium [12].

Associations of Mivazerol with other chemical compounds

• The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia [13].
• CONCLUSION: The present study demonstrates that emergence from halothane anesthesia increases i.t. release of GLU, and that mivazerol has an inhibitory effect on the above, through its direct action on the spinal cord [14].

Analytical, diagnostic and therapeutic context of Mivazerol

• Effects of immobilization stress on hippocampal monoamine release: modification by mivazerol, a new alpha 2-adrenoceptor agonist [15].
• Control hearts (n = 13) were not treated; two groups were treated with the H3-agonist R-alpha-methyl-histamine at 0.3 microM (n = 14) and 1 microM (n = 11) and one group, used as positive control, was treated with the selective alpha 2-agonist Mivazerol at 0.5 microM (n = 14) added to the perfusion medium [16].
• To investigate this issue, the effects of mivazerol on the pressor, systemic and regional hemodynamic (pulsed Doppler technique) as well as on the cardiac responses to electrical stimulation of the spinal cord (SCS) were measured in pithed rats in the absence and in the presence of mivazerol [11].
• Ischaemic injury in a number of animal models is reduced by mivazerol (2-hydroxy-3-[(1-H-imidazol-4-yl) methyl]-benzamide, CAS 125472-02-8) [17].
• This expectation has been corroborated in clinical trials with clonidine, dexmedetomidine and mivazerol and meta-analyses; additional large controlled trials would be instructive in establishing a robust estimate of the scale of the benefit [18].

References