Administration Of Metaraminol Research Articles

Meningismus after metaraminol administration in a patient with Familial Mediterranean fever

Meningismus after metaraminol administration in a patient with Familial Mediterranean fever

GABA-mediated attenuation of noradrenaline release in the rat median preoptic area caused by intravenous injection of metaraminol

Previous studies have shown that the noradrenergic system in the median preoptic nucleus (MnPO) play an important role in the control of the body fluid balance and cardiovascular function and that the release of noradrenaline in the MnPO is regulated by γ-aminobutyric acid (GABA) receptor mechanisms. The present study was carried out to examine whether the GABAergic system is involved in the modulation of the noradrenaline release in the MnPO in response to an elevation in blood pressure using in vivo microdialysis techniques. In urethane-anaesthetised male rats, the rise in arterial pressure caused by intravenous administration of the α-agonist metaraminol significantly decreased dialysate noradrenaline concentration in the MnPO area. The decrease in the noradrenaline level elicited by the metaraminol administration was significantly attenuated by perfusion with either bicuculline (10 μM), a GABA A receptor antagonist, or phaclofen (10 μM), a GABA B receptor antagonist, through a microdialysis probe. The amount of the antagonist-induced attenuation was much greater in the bicuculline-treated group than in the phaclofen-treated group. These results suggest that the release of noradrenaline in the MnPO area may be modulated by neural inputs from the peripheral baroreceptors, and that the neural inputs may be mediated in part through GABA A receptors rather than GABA B receptors in the MnPO area.

Alpha1-adrenoceptor stimulation enhances experimental gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of the norepinephrine-mimicking agent metaraminol, the alpha1-adrenergic agonist phenylephrine and the alpha2-adrenergic agonist clonidine on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ornithine decarboxylase activity of the gastric cancer and the labeling index of the gastric mucosa were investigated in Wistar rats. Rats received s.c. injections of metaraminol, phenylephrine or clonidine every other day after 20 weeks of oral treatment with MNNG. At week 52, administration of metaraminol and phenylephrine at the higher dose significantly increased the incidence of gastric cancers, the ornithine decarboxylase activity of the gastric cancers and the labeling index of the antral epithelial cells. Administration of phenylephrine at the lower dose and clonidine at both doses had no significant effect on the incidence of gastric cancers, the ornithine decarboxylase activity of the gastric cancers or the labeling index of the gastric mucosa. Our results suggest that adrenoreceptor stimulation enhances gastric carcinogenesis and that such enhancement is mediated through alpha1-adrenoceptors without alpha2-adrenoceptor involvement.

Effect of metaraminol during acute inferior wall myocardial infarction accompanied by hypotension: Preliminary study

This study was designed to evaluate the effects of metaraminol (Aramine) in six patients with evolving acute inferior wall myocardial infarction accompanied by hypotension and warm limbs. There were 16 episodes of acute inferior wall ischemia, and the response to therapy was judged by evaluating blood pressure and ST segment and T wave abnormalities. Three patients received intravenous isosorbide dinitrate and two received streptokinase as the initial therapy. The mean ST segment elevation was significantly reduced (from 4.94 +/- 1 to 0.5 +/- 0.7 [p less than 0.0001]) after metaraminol infusion was initiated. The average T wave height also decreased (from 6.8 +/- 2 to -1.3 +/- 2.5 mm [p less than 0.0005]). The average heart rate decreased from 82 +/- 11 to 69 +/- 9 beats/min (p less than 0.05) and the mean arterial blood pressure increased from 81 +/- 12 mm Hg before metaraminol treatment to 126 +/- 8 mm Hg after treatment. All these changes occurred within a few minutes after metaraminol therapy was instituted. In 12 episodes, accelerated idioventricular rhythm appeared concomitantly with the resolution of ST segment elevation. Coronary angiography performed between 4 and 10 days after admission demonstrated significant obstruction in all infarct-related arteries, but none was totally occluded. Left ventricular function was normal in three patients and slightly hypokinetic in the inferior wall in two. These results indicate that in a selected group of patients with acute inferior myocardial infarction, metaraminol administration (in certain hemodynamic circumstances) can alleviate acute ischemia within a few minutes and thereby reduce ischemic injury.

Central action of beta-phenylethylamine derivatives. (7) Effects of intracerebral administration of tyramine on brain monoamine levels in mice

Effects of intracerebral (i.c.) administration of metaraminol (MA) on brain monoamine in mice were studied. The results were as follows: MA, dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were separated with phosphate buffer using a phosphorylated cellulose column (1X11 cm, 9 ml, Lot No. 2809). When MA was i.c. injected into mice, fluorescence of MA at 275/305 nm decreased in proportion to the time course and remained even at 12 hr after injection. Thirty min after MA in doses of either 40 or 80 microgram, a significant decrease of DA as compared with that of saline-treated group occurred and MA, in doses of 40, 80 and 160 microgram produced a significant decrease of NA and 5-HT. Thirty min after 160 microgram of MA, there was no significant difference in DA. Three hr after MA, DA levels significantly decreased, and 168 hr after were restored to the levels of the saline-treated group. Thirty min after MA, NA and 5-HT signficantly decreased compared with those of the saline-treated group and recovery took place 48 hr and 168 hr after respectively. It was concluded that MA depletes not only NA but also DA and 5-HT in the mouse brain.

Antagonistic effects of alpha and beta-adrenergically coded hypothalamic neurones on consummatory behaviour in the rat.

IN the past 5 years, we have demonstrated the diametrically opposite effects of alpha-adrenergic and beta-adrenergic amines on water balance in the albino rat. Isoproterenol, a beta-adrenergic agonist, when injected subcutaneously in single doses of 0.05–5.25 mg/kg body weight, produced in animals sated with water a copious drinking and simultaneous inhibition of the urine flow lasting about 3 h. In contrast with this paradoxical phenomenon, the administration of metaraminol, an alpha-adrenergic agonist, induced a water depleting reaction. Rats subcutaneously injected with 0.63–10.0 mg/kg body weight of metaraminol excreted large volumes of dilute urine but made no immediate efforts towards recouping this massive water loss by drinking. Both the water depleting and water sparing response could be obviated readily by treating the rats with equimolecular quantities of either alpha or beta-adrenergic blocking agents before administration of the respective agonist. These findings seemed to be consistent with the existence of central nervous system circuits of water regulation which are chemically coded to respond in antagonistic fashion to selective alpha or beta-adrenergic stimulation1.

Angiotensin-catecholamine interactions in the rabbit

The effects of angiotensin and metaraminol on myocardial uptake of 3H-norepinephrine in the isolated perfused heart and the in vivo effects of angiotensin on myocardial norepinephrine levels were studied. Inhibition of 3H-norepinephrine uptake resulted with angiotensin and metaraminol administration. Immediately after the administration of angiotension in vivo, endogenous myocardial norepinephrine levels were transiently increased. This increase in myocardial norepinephrine content was inversely related to the dose of angiotensin administered and was abolished by acute bilateral adrenalectomy. Angiotensin-induced stimulation of catecholamine release was investigated in the isolated, retrograde perfused adrenal. Dose-dependent stimulation of adrenal catecholamine secretion was observed. The data substantiate the ability of angiotensin to modulate sympathoadrenal function.

Displacement of norepinephrine from the rat heart by 14C-metaraminol

Rats were injected with submaximal quantities (0.24 mg/kg) of 14C-metaraminol, i.e. enough to lower the concentration of norepinephrine in the heart by about 60 per cent, measured 18 hr after drug administration. In the ventricles at 18,42 and 66 hr after metaraminol injection and in the atria at the two latter times, radioactivity was present in amounts sufficient to account exactly for the norepinephrine missing, on a mole-for-mole displacement basis. Atrial radioactivity 18 hr after metaraminol administration was insufficient to account for the whole of the missing catecholamine. Possibly at 18 hr a steady state had not been reached in the atria, an interpretation which is strengthened by the fact that other catecholamines (epinephrine and dopamine) were present only in trace amounts. Chemically determined metaraminol was consistently less than indicated by radiocounting. Even though no evidence was gained for the presence of 14C-α-methylnorepinephrine in the tissue, it is possible that metabolites of metaraminol account for part of the norepinephrine displacement observed. The administration of larger amounts of 14C-metaraminol (3 mg/kg) resulted in catecholamine depletion greater than that accounted for by radio-activity in the tissue, and this was particularly striking in the atria. Thus, the relationship between tissue radio-activity and norepinephrine concentration depends upon several factors, and only under certain conditions, as described above, is a one-for-one displacement of the catecholamine clearly demonstrated.

Isoproterenol in the Treatment of Shock Due to Bacteremia with Gram-Negative Pathogens

A series of 12 patients with shock that followed bacteremia due to gram-negative pathogens is presented, and a case is reported. The hemodynamic alterations that occur in such patients are discussed. Initial therapy includes intravascular volume expansion and administration of glucocorticoids and antibiotic drugs; subsequent therapy, if necessary, includes administration of metaraminol and isoproterenol respectively. The problems encountered with this method of treatment are described. The use of isoproterenol (2.5 to 5 mg. in 500 ml. of 5 per cent dextrose in water administered intravenously at a rate of 0.5 to 2.0 ml. per minute) is suggested to correct the hemodynamic alterations usually present and permit further expansion of circulating blood volume with reduced risk of acute circulatory overload. Clinical use of this drug is recommended because of its positive ionotropic effect on the myocardium (beta-adrenergic stimulation) and direct peripheral arterial vasodilator effect (alpha-adrenergic blockade) that act to correct the hemodynamic alterations usually present in man in endotoxin shock.

Hemodynamic effects of vasopressor agents in hemorrhagic shock

In experimental hemorrhagic shock there is a decline in blood flow to all organs and tissues of the body. Of the regions studied, there is initially less decline in flow to tissues supplied by the renal and superior mesenteric arteries and more to those supplied by the carotid and femoral arteries. Administration of metaraminol and norepinephrine may be effective in partially restoring blood flow, but with the degree of hypovolemia produced in these experiments, regional blood flow did not return to normal when blood pressure was raised to the control level. Metaraminol, in the experimental setting used, was more effective in partially restoring blood flow than norepinephrine. In human hemorrhagic shock, vasopressors should be used only as necessary in conjunction with replacement of blood volume and attempts to stop hemorrhage, and after careful consideration of their hemodynamic properties.