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Chemical Compound Review

Vasoxine     2-amino-1-(2,5- dimethoxyphenyl)propan-1-ol

Synonyms: Vasoxin, Vasoxyl, Methoxamin, Metoxamina, Metossamina, ...
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Disease relevance of methoxamine


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


Chemical compound and disease context of methoxamine


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


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].


  1. Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function. Cabanes, L., Costes, F., Weber, S., Regnard, J., Benvenuti, C., Castaigne, A., Guerin, F., Lockhart, A. N. Engl. J. Med. (1992) [Pubmed]
  2. Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats. Sheridan, D.J., Penkoske, P.A., Sobel, B.E., Corr, P.B. J. Clin. Invest. (1980) [Pubmed]
  3. Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis. Heller, J., Schepke, M., Gehnen, N., Molderings, G.J., Müller, A., Erhard, J., Spengler, U., Sauerbruch, T. Gastroenterology (1999) [Pubmed]
  4. Protection of ischemic myocardium by nitroglycerin: experimental and clinical results. Epstein, S.E., Borer, J.S., Kent, K.M., Redwood, D.R., Goldstein, R.E., Levitt, B. Circulation (1976) [Pubmed]
  5. Role of central alpha-1 adrenoceptors in canine narcolepsy. Mignot, E., Guilleminault, C., Bowersox, S., Rappaport, A., Dement, W.C. J. Clin. Invest. (1988) [Pubmed]
  6. Effects of methoxamine and alpha-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat. Pellejero, T., Monti, J.M., Baglietto, J., Jantos, H., Pazos, S., Cichevski, V., Hawkins, M. Sleep. (1984) [Pubmed]
  7. Effects of intrathecal alpha1- and alpha2-noradrenergic agonists and norepinephrine on locomotion in chronic spinal cats. Chau, C., Barbeau, H., Rossignol, S. J. Neurophysiol. (1998) [Pubmed]
  8. Lack of delayed effects of amphetamine, methoxamine, and prazosin (adrenergic drugs) on behavioral outcome after lateral fluid percussion brain injury in the rat. Dose, J.M., Dhillon, H.S., Maki, A., Kraemer, P.J., Prasad, R.M. J. Neurotrauma (1997) [Pubmed]
  9. Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis. Egashira, K., Pipers, F.S., Morgan, J.P. J. Clin. Invest. (1991) [Pubmed]
  10. Effect of nitroglycerin and dipyridamole on regional left ventricular blood flow during coronary artery occlusion. Becker, L.C. J. Clin. Invest. (1976) [Pubmed]
  11. Is epinephrine contraindicated during cardiopulmonary resuscitation? Thrush, D.N., Downs, J.B., Smith, R.A. Circulation (1997) [Pubmed]
  12. Alpha 1-adrenergic inhibition of the beta-adrenergically activated Cl- current in guinea pig ventricular myocytes. Oleksa, L.M., Hool, L.C., Harvey, R.D. Circ. Res. (1996) [Pubmed]
  13. The role of arterial baroreceptors in the regulation of arterial pressure in conscious dogs. McRitchie, R.J., Vatner, S.F., Heyndrickx, G.R., Braunwald, E. Circ. Res. (1976) [Pubmed]
  14. Microvascular mechanisms of change in tumor blood flow due to angiotensin II, epinephrine, and methoxamine: a functional morphometric study. Hori, K., Zhang, Q.H., Saito, S., Tanda, S., Li, H.C., Suzuki, M. Cancer Res. (1993) [Pubmed]
  15. The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats. Lee, F.Y., Albillos, A., Colombato, L.A., Groszmann, R.J. Hepatology (1992) [Pubmed]
  16. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Tsai, M.H., Iwakiri, Y., Cadelina, G., Sessa, W.C., Groszmann, R.J. Gastroenterology (2003) [Pubmed]
  17. Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats. Hennenberg, M., Biecker, E., Trebicka, J., Jochem, K., Zhou, Q., Schmidt, M., Jakobs, K.H., Sauerbruch, T., Heller, J. Gastroenterology (2006) [Pubmed]
  18. Left ventricular function after repair of tetralogy of fallot and its relationship to age at surgery. Borow, K.M., Green, L.H., Castaneda, A.R., Keane, J.F. Circulation (1980) [Pubmed]
  19. Disparity between ejection and end-systolic indexes of left ventricular contractility in mitral regurgitation. Berko, B., Gaasch, W.H., Tanigawa, N., Smith, D., Craige, E. Circulation (1987) [Pubmed]
  20. Mechanisms for the positive inotropic effect of alpha 1-adrenoceptor stimulation in rat cardiac myocytes. Fedida, D., Bouchard, R.A. Circ. Res. (1992) [Pubmed]
  21. Role of endothelium in the abnormal response of mesenteric vessels in rats with portal hypertension and liver cirrhosis. Atucha, N.M., Shah, V., García-Cardeña, G., Sessa, W.E., Groszmann, R.J. Gastroenterology (1996) [Pubmed]
  22. Focal smooth muscle proliferation in the aortic intima produced by an initiation-promotion sequence. Majesky, M.W., Reidy, M.A., Benditt, E.P., Juchau, M.R. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  23. Effects of pharmacologically-induced hypertension on myocardial ischemia and coronary hemodynamics in patients with fixed coronary obstruction. Loeb, H.S., Saudye, A., Croke, R.P., Talano, J.V., Klodnycky, M.L., Gunnar, R.M. Circulation (1978) [Pubmed]
  24. Depressed responsiveness to vasoconstrictor and dilator agents and baroreflex sensitivity in conscious, newborn lambs. Manders, W.T., Pagani, M., Vatner, S.F. Circulation (1979) [Pubmed]
  25. Right atrial pressure-volume relationships in tricuspid regurgitation. Miller, M.J., McKay, R.G., Ferguson, J.J., Sahagian, P., Nakao, S., Come, P.C., Grossman, W. Circulation (1986) [Pubmed]
  26. Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats. Wiest, R., Tsai, M.H., Groszmann, R.J. Gastroenterology (2001) [Pubmed]
  27. Pulmonary ventilation/perfusion defects induced by epinephrine during cardiopulmonary resuscitation. Tang, W., Weil, M.H., Gazmuri, R.J., Sun, S., Duggal, C., Bisera, J. Circulation (1991) [Pubmed]
  28. Contractile performance of the hypertrophied ventricle in patients with systemic hypertension. Takahashi, M., Sasayama, S., Kawai, C., Kotoura, H. Circulation (1980) [Pubmed]
  29. The linearity of the end-systolic pressure-volume relationship in man and its sensitivity for assessment of left ventricular function. Mehmel, H.C., Stockins, B., Ruffmann, K., von Olshausen, K., Schuler, G., Kübler, W. Circulation (1981) [Pubmed]
  30. Role of the eNOS Glu298Asp variant on the GNB3825T allele dependent determination of alpha-adrenergic coronary constriction. Naber, C.K., Baumgart, D., Heusch, G., Siffert, W., Oldenburg, O., Huesing, J., Erbel, R. Pharmacogenetics (2003) [Pubmed]
  31. Endothelium-dependent vascular activities of endothelin-like peptides in the isolated superior mesenteric arterial bed of the rat. Douglas, S.A., Hiley, C.R. Br. J. Pharmacol. (1990) [Pubmed]
  32. Oxytocin augments baroreflex bradycardia in conscious rats. Russ, R.D., Walker, B.R. Peptides (1994) [Pubmed]
  33. A mitogen-activated protein kinase is involved in the inotropic but not chronotropic actions of adrenoceptor agonists and endothelin-1. Peters, S.L., Sand, C., Michel, M.C., Pfaffendorf, M., Van Zwieten, P.A. Naunyn Schmiedebergs Arch. Pharmacol. (2002) [Pubmed]
  34. Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers. Graupera, M., García-Pagán, J.C., Abraldes, J.G., Peralta, C., Bragulat, M., Corominola, H., Bosch, J., Rodés, J. Hepatology (2003) [Pubmed]
  35. Acute arterial hypertension during spontaneous angina in patients with fixed coronary stenosis and exertional angina: an associated rather than a triggering phenomenon. Figueras, J., Cinca, J. Circulation (1981) [Pubmed]
  36. Doppler and electromagnetic comparisons of instantaneous aortic flow characteristics in primates. Spencer, K.T., Lang, R.M., Neumann, A., Borow, K.M., Shroff, S.G. Circ. Res. (1991) [Pubmed]
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