Disease relevance of methoxamine

• In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03) [1].
• The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction [1].
• Intracoronary methoxamine (0.1 microM) in animals depleted of myocardial catecholamines by 6-hydroxydopamine pretreatment did not affect idioventricular rate before coronary occlusion [2].
• RESULTS: Maximal methoxamine-induced contractions were reduced in cirrhotic hepatic arteries (cirrhosis, 51.8% +/- 6.8%; donor, 89.9% +/- 6.6%; P < 0.01) and portal veins (cirrhosis, 49.2% +/- 6.4%; donor, 94.0% +/- 5.3%; P < 0.01) [3].
• This salutary effect occurs despite lowering of systemic arterial pressure, as long as excessive reflex tachycardia does not result; the magnitude of ischemia reduction is potentiated when methoxamine or phenylephrine are administered simultaneously to abolish the NTG -induced hypotension and reflex tachycardia [4].

Psychiatry related information on methoxamine

• Treatment of narcoleptic dogs with 25-600 micrograms/kg prazosin, a selective alpha-1 adrenergic receptor blocker, exacerbated cataplexy, whereas treatment with the alpha-1 agonist, methoxamine, ameliorated it [5].
• Methoxamine (4-8 mg/kg), an alpha 1-adrenoceptor agonist, induced a dose-related increase in wakefulness (W) and a decrease in slow-wave sleep (SWS) and REM sleep (REMS) [6].
• The alpha1 agonist methoxamine induced bouts of nice locomotor activity in three spinal cats some hours after injection but only induced sustained locomotion in one cat in which the effects were blocked by the alpha1 antagonist prazosin [7].
• Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals [8].

High impact information on methoxamine

• Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction [1].
• In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption [1].
• Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function [1].
• Under in vitro conditions where isometric force of isolated ring segments was measured, methoxamine (an alpha 1 agonist) or BHT-920 (an alpha 2 agonist) produced similar degrees of contraction of denuded and control vessels; however, cocaine in concentrations up to 3 x 10(-3) M did not produce contraction [9].
• These data indicate that both types of coronary vasodilators, when used in conjunction with methoxamine to support blood pressure, reduce collateral resistance, increase collateral flow, and reduce epicardial ST-segment elevations [10].

Chemical compound and disease context of methoxamine

• CONCLUSIONS: During experimental ventricular fibrillation and CPR, epinephrine increased intrapulmonary shunt approximately 300% more than saline or methoxamine and significantly reduced arterial oxygen saturation [11].
• However, methoxamine inhibition of the isoproterenol-activated Cl- current was sensitive to pertussis toxin [12].
• Pressure was altered by intravenous bolus injections and continuous infusions of nitroglycerin and methoxamine and also by hemorrhage [13].
• Arteriolar pressure in each segment both under normotension and under hypertension induced by angiotensin II, epinephrine, or methoxamine was measured using a microocclusion technique [14].
• We performed dose-response curves to methoxamine, an alpha-adrenoceptor agonist, with and without N omega-nitro-L-arginine, a specific inhibitor of nitric oxide synthesis, in experimental portal hypertension [15].

Biological context of methoxamine

• Effects of vasoconstriction of the SMA in PVL and RAL rats were evaluated by measuring perfusion pressure changes in isolated SMA beds in response to methoxamine, nitric oxide synthase activity, and eNOS protein expression [16].
• Methoxamine-induced activation of RhoA as well as basal and methoxamine-induced phosphorylation of moesin were strongly reduced in aortas from cirrhotic rats [17].
• Left- and right-heart hemodynamics were measured at various levels of afterload induced by methoxamine while heart rate was maintained constant [18].
• In eight anesthetized open-chest dogs, pressure-volume loops were derived during afterload manipulation with methoxamine and nitroprusside from simultaneous left ventricular pressure and dimensional (sonomicrometry techniques) data before and after creation of MR [19].
• At 22-23 degrees C the specific alpha 1-adrenoceptor agonist methoxamine (100 microM) prolonged action potential duration at 50% repolarization from 55 +/- 2 to 81 +/- 5 msec, delayed time to peak contraction, and increased shortening amplitude from 5.3 +/- 0.6 to 7.8 +/- 1 microns (n = 18) [20].

Anatomical context of methoxamine

• The aim of this study was to evaluate the role of vascular endothelium in the hyporesponsiveness to methoxamine (MTX) in the mesenteric vascular bed of portal vein-ligated (PVL) and cirrhotic rats [21].
• Scanning electron microscopy revealed small mound-like lesions protruding from an intact endothelium in birds treated with an initiating dose of 7,12-dimethylbenz[a]anthracene (Me2BA) followed by twice weekly injections of the alpha 1-selective adrenergic agonist methoxamine for 20 weeks [22].
• Twenty patients with fixed coronary artery obstruction were studied during rapid atrial pacing and methoxamine infusion [23].
• Finally, the sensitivity of the arterial baroreceptor reflex was evaluated by comparing the regression of pulse interval (PI) on systolic arterial pressure (SAP) after an intravenous dose of methoxamine in conscious, adult and newborn animals [24].
• Increased right ventricular afterload mediated by constriction of the pulmonary artery and infusion of methoxamine reversibly converted the right atrial pressure-volume loop from that of mild to that of severe tricuspid regurgitation [25].

Associations of methoxamine with other chemical compounds

• With the addition of methoxamine in both dilator groups, blood pressure returned to base line while flow to ischemic areas increased above base-line values (TNG, 0.16-0.20 ml/min per g, P less than 0.01; dipyridamole, 0.18-0.31 ml/min per g, P less than 0.05) [10].
• METHODS: In vitro-perfused SMA vascular beds were tested for the cumulative dose-response to octreotide at baseline conditions and after preconstriction with different vasoconstrictors (alpha1-agonist methoxamine, endothelin [ET-1], phorbol ester [PdBu], and potassium chloride [KCl]) [26].
• Epinephrine and methoxamine but not saline placebo significantly increased coronary perfusion pressure from approximately 32 to 55 mm Hg [27].
• The WSt-diameter relation obtained during dynamic responses to acute pressure reduction by nitroprusside infusion was compared with the same relation obtained in 10 normal subjects (posterior wall thickness averaged 0.7 cm [range 0.6-0.9 cm]) over a range of matched systolic pressure induced by methoxamine administration [28].
• Three ventriculograms were performed: at rest, after oral isosorbide dinitrate, 10 mg (systolic pressure decrease greater than or equal to 15 mm Hg), and during infusion of methoxamine, 2 mg/min (systolic pressure increase greater than or equal to 10 mm Hg) [29].

Gene context of methoxamine

• Genotyping at the GNB3 and the eNOS gene was performed on 48 individuals receiving either the alpha(1)-adrenoceptor agonist methoxamine (5 mg i.c.) and/or the alpha(2)-adrenoceptor agonist BHT 933 (5 mg i.c.). CBF was calculated from quantitative coronary angiography and intracoronary Doppler flow velocity measurement [30].
• Finally, the direct vasodilator properties of endothelin-2, endothelin-3 and sarafotoxin S6b were studied in preparations preconstricted with methoxamine [31].
• Infusion of oxytocin at a dose that had no effect on baseline hemodynamic values significantly augmented the bradycardic response to IV bolus doses of methoxamine [32].
• Inotropic and chronotropic responses of the isolated atria to methoxamine, isoprenaline and endothelin-1 were measured in the absence and presence of inhibitors of MAPK pathways [33].
• In conclusion, COX-derived prostanoids, mainly TXA(2), play a major role in regulating the response of cirrhotic livers to methoxamine [34].

Analytical, diagnostic and therapeutic context of methoxamine

• Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design [1].
• In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance) [1].
• However, early after coronary reperfusion, methoxamine increased idioventricular rate from 33 +/- 7 to 123 +/- 21 beats/min (P less than 0.01) [2].
• After documentation of the electrocardiographic and arterial blood pressure changes during two or more episodes of resting angina, i.v. methoxamine was infused under continuous monitoring of the ECG, arterial blood pressure and pulmonary artery diastolic pressure [35].
• Accordingly, data from electromagnetic flow and continuous-wave aortic Doppler recordings were simultaneously acquired and compared in five monkeys over a wide range of flows generated by intravenous infusions of the beta-adrenoceptor agonist dobutamine and the alpha-receptor agonist methoxamine [36].

References