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PubMed1977

Metaraminol uptake by human thrombocytes: a poor model for neuronal noradrenaline uptake.

The IC50 of a number of antidepressants and related drugs on the uptake of 1-metaraminol and serotonin into human thrombocytes, and of noradrenaline and serotonin into rat midbrain synaptosomes were compared. In accordance with previous reports, it was found that platelets provide a good model for the study of neuronal uptake of serotonin. Platelet uptake of 1-metaraminol, although correlated to some extent with noradrenaline uptake into synaptosomes, seems to be an unsatisfactory model for the neuronal uptake of the latter amine.

Animals↗
PubMed1984

Metaraminol and dobutamine for the treatment of hypotension associated with epidural block.

In 14 patients undergoing major abdominal surgery, epidural analgesia was performed and cardiovascular changes were examined by insertion of Swan-Ganz catheters. To counteract the hypotensive episodes associated with epidural block, Dobutamine (1-3 micrograms/kg body wt min-1) and Metaraminol (0.5-1.5 micrograms/kg body wt min-1) in various doses were infused and the effects of these vasoactive agents were examined. Epidural analgesia decreased arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure and central venous pressure associated with marked decrease in cardiac index, stroke volume index, left ventricular and right ventricular stroke work without changes in systematic vascular resistance, pulmonary vascular resistance or heart rate. The infusion of Metaraminol caused a marked increase in arterial pressure, pulmonary arterial pressure, wedge pressure and central venous pressure. Calculated variables of stroke volume, systemic vascular resistance, left and right stroke work and cardiac work increased significantly. The infusion of Dobutamine caused a marked increase in arterial and pulmonary arterial pressure, wedge pressure, central venous pressure and cardiac index associated with those calculated changes of left and right stroke work and cardiac work, which were increased markedly. On the other hand, heart rate, stroke volume and pulmonary vascular resistance did not show any remarkable changes. Our study indicates that the fall in arterial blood pressure associated with epidural block may be due to marked decrease in cardiac output, and the infusion of Dobutamine is one of the desirable methods to counteract the hypotensive episode.

Adult↗
PubMed2004

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 gamma-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 alpha-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 microM), a GABA(A) receptor antagonist, or phaclofen (10 microM), 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.

Adrenergic alpha-Agonists↗
PubMed1984

Metaraminol provocative test: a specific diagnostic test for familial Mediterranean fever.

The diagnosis of familial Mediterranean fever has been one of exclusion. In a placebo-controlled, double-blind, cross-over study a challenge with a 10 mg dose of metaraminol infusion was followed within 48 h by a typical disease-like attack in all of 21 patients with familial Mediterranean fever but in none of 21 control subjects. The induced attacks were milder and of shorter duration than the spontaneous ones. The metaraminol-induced symptoms were similar to the natural disease attacks and could be prevented with prophylactic colchicine therapy. No significant side-effects were observed.

Adolescent↗
PubMed1999

A study to determine the optimum dose of metaraminol required to increase blood pressure by 25% during subarachnoid anaesthesia.

We studied dosage optimization for metaraminol when managing hypotension during subarachnoid anaesthesia. Twenty patients aged 53 to 84 years, were recruited. Non-invasive blood pressure (BP) and heart rate were recorded one-minutely. A series of four i.v. metaraminol boluses (0.25 to 1.0 mg per 50 kg adult) were administered. From individual patient time plots of BP predicted dosages for a 25% elevation in BP were estimated. Dose-related elevations in systolic BP [mean (SD)] occurred following dosages of 0.5 mg [25 (11)%] and 1.0 mg [50 (23)%]. Similar elevations occurred in mean and diastolic BP. Overall estimated dosage (median) to produce a 25% elevation in systolic BP was 0.5 mg (per 50 kg adult). However, individual patient responses varied (10-90th centiles = 0.23 to 0.80 mg). Thus, we now recommend a starting dose of 0.25 mg, increasing to 0.5 mg if necessary, to treat hypotension (25% decrease in systolic BP) during subarachnoid anaesthesia.

Aged↗
PubMed1979

Effects of intraventricularly administered serotonin, noradrenaline, dopamine and metaraminol on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits.

Effects of intraventricularly administered serotonin (5HT), noradrenaline (NA), dopamine (DA) and metaraminol on the reserpine-induced spikes recorded from the medial nucleus Trapezoides (Trap. m.) in rabbits were investigated. 5HT (30, 50 micrograms) produced marked decreases in the amplitude and discharge rate of the spikes 3 to 5 min after intraventricular administration. NA (30, 50 micrograms) also produced similar effects to those of 5HT, but DA at the same dosage produced no significant changes in the amplitude and discharge rate of spikes. Metaraminol, a metabolite of alpha-methyl-m-tyrosine, produced gradual and long-lasting, potent suppression of spikes. Ninety min later, spikes were completely suppressed, and no recovery was observed within 6 hours after intraventricular administration. These results indicate that NA has a similar suppressing action to that of 5HT on the generation of the reserpine-induced spikes.

Action Potentials↗
PubMedDate not supplied

Successful management of stuttering priapism using home self-injections of the alpha-agonist metaraminol.

Low-flow priapism can result in impotence if treatment is delayed, yet patients with recurrent priapism often suffer delay before therapy. We describe management of recurrent priapism using self-administered injections of intracavernosal metaraminol (Aramine, Merck), a long-acting vasoconstricting amine that is considered safer than epinephrine. The patient injects as often as once daily using 5-10 mg of drug. Our patient reports rapid detumescence and has not required emergency room visits since starting injections. He denies complications. Treatment of priapism using metaraminol has been suggested in the hospital setting; however, this is the first report of successful home self-administration of the drug.

Adult↗
PubMed1975

Characteristics of uptake of [3-H](plus or minus)-metaraminol by human fallopian tube.

The characteristics of accumulation of 5 X 10 minus8M [3-H] (plus or minus)-metaraminol were studied in isolated human fallopian tube. In both the ampulla and isthmus, the amine was concentrated against the concentration gradient; Accumulation was inhibited by noradrenaline, cocaine, and ouabain but not by oxytetracycline or normetanephrine. It was concluded that [3-H] (plus or minus)-metaraminol was accumulated in the adrenergic nerves present in the human fallopian tube.

Cocaine↗
PubMed1975

Uptake and release of 3H-metaraminol by rat lung. The influence of various drugs.

Uptake and release of 3H-metaraminol was measured in vitro incubating rat lung tissue in the presence of ouabain (1.5-45 mug/ml), cocaine (1-30 mug/ml), tyramine (0.1-3 mug/ml, reserpine (0.05-1.5 mug/ml), imipramine (0.1-3 mug/ml) and desipramine (0.3-10 mug/ml. All drugs significantly inhibited uptake and release of 3H-metaraminol from lung tissue. This blockade most probably occurs at membrane levels of both neuronal uptake-1 sites and extraneuronal uptake-2 sites. These results further emphasize the importance of the lung in the fate of drugs and endogenous substances.

Animals↗
PubMed1976

[Correction of the alphamimetic effects of metaraminol by nicergoline].

In this work, the authors are studying the cardio-vascular effects of nicergoline. To do so, the drug is made to compete with metaraminol whose dominant alphamimetic effects are known. This experimentation was performed in 7 patients in coma stage III or IV and whose vascular receptors were active. Those 7 patients were submitted continuous metaraminol perfusion and a steady state vasoconstriction was thus obtained. A single intravenous injection of 10 mg nicergoline resulted in vasodilation with a fall in vascular resistance and a moderate fall in mean blood pressure. Cardiac output remained unchanged. This work confirme thus the alphasympatholytic effects of nicergoline.

Blood Pressure↗
PubMed1986

[Metaraminol--an antidote in corpus cavernosum autoinjection therapy-induced prolonged erection].

Up to now 65 patients with erectile dysfunction were treated by means of corpus cavernosum-autoinjection-therapy (CAT). The only side effect observed were 6 prolonged erections, which could successfully be treated in 3 cases by puncture and aspiration of the corpora cavernosa. In another 3 cases prolonged erection subsided after an intracavernous injection of 2 mg metaraminol. Erection induced by CAT was immediately interrupted by metaraminol in 10 other patients.

Adult↗
PubMed1965

Effects of a combination of atropine, metaraminol and pyridine aldoxime methanesulfonate (AMP therapy) on normal human subjects.

Four hundred and seventeen medical students at the University of Toronto were used as both subjects and observers in a series of double-blind experiments to determine possible toxic effects following oral ingestion of various combinations of 2 mg. atropine, 10 mg. metaraminol and 1 g. pyridine aldoxime methanesulfonate (P(2)S). Heart rate, blood pressure, pupil diameter, and visual accommodation were measured before and at 20-minute intervals after drug administration for 100 minutes. A visual and memory perceptual test (Mackworth) was performed before and 100 minutes after drug ingestion.No toxic effects were observed following administration of the triple combination of atropine, metaraminol and P(2)S (AMP therapy). The AMP combination might be useful prophylactically for persons facing exposure to organophosphorus anticholinesterase compounds. It must not be considered an adequate substitute for treatment should poisoning occur.

Atropine↗
PubMed1976

Effects of metaraminol, insulin and trasylol on the responses to haemorrhage in dogs.

The effect of addition of metaraminol, insulin and trasylol to fluid replacement with glucose-saline, on the responses to haemorrhage (30% of blood volume) in dogs, was investigated. Addition of metaraminol significantly increased the blood sugar and lactate responses to haemorrhage; the lactate-pyruvate (L/P) ratio, plasma phosphate and free fatty acid (FFA) levels were also significantly increased. A delayed hypotension was observed. Responses to haemorrhage during infusion of glucos-saline + insulin showed reduced blood sugar, blood lactate, pyruvate, and L/P ratios, plasma inorganic phosphate and FFA were diminished while, mean arterial blood pressure (MABP) changes were significantly higher than the glucose-saline group. Infusion of trasylol in glucose-saline did not significantly affect the blood sugar, lactate, and pyruvate resonses and the L/P ratio. Plasma phosphate response was also like the control group. The responses of plasma FFA and of MABP in this group were significantly higher than glucose-saline group. The mechanisms of these effects and the significance of thse results are discussed.

Animals↗
PubMed1988

Mollaret's meningitis. A variant of recurrent hereditary polyserositis, both provoked by metaraminol.

Mollaret's meningitis is a rare condition with a characteristic clinical and cerebrospinal fluid picture. In many ways it resembles recurrent hereditary polyserositis (familial Mediterranean fever) in its natural history, pattern of attacks, and response to colchicine. Association of the two conditions has been reported, so far, in two patients only. In our patient the symptoms of both conditions were induced by a metaraminol provocative infusion. We have previously introduced this as a specific diagnostic and confirmatory test for recurrent hereditary polyserositis. The possibility that the two conditions represent different manifestations of a single disease is therefore strengthened.

Adolescent↗
PubMed1977

Relationship between the uptake of 3H-(+/-)metaraminol and the density of adrenergic innervation in isolated rat tissues.

1. The uptake of 3H-(+/-)metaraminol (MA) by tissue slices or pieces was studied in vitro in several peripheral rat organs of varying density of sympathetic innervation (the tissue level of endogenous noradrenaline ranging from 1.7-99.1 nmoles/g). In each individual tissue preparation amine uptake was corrected for entry into the 14C-D-sorbitol space. 2. When the tissues were incubated with 1.4 muM MA, the rate of total amine uptake (i.e., neuronal plus extraneuronal uptake of MA) remained virtually constant for up to 7 min. Therefore, rates of uptake were determined after 2 min of incubation with substrate concentrations ranging from 0.25-12.2 muM. In all tissues the total uptake of MA was saturable. 3. Under the condition of inhibition of neuronal uptake by the presence of 100 muM cocaine, the uptake of MA (considered as extraneuronal amine uptake) was no longer saturable. When tissues were exposed to 1.4 muM MA, the relative contribution by extraneuronal (measured in the presence of cocaine) to total amine uptake (measured in the absence of cocaine) was inversely correlated with the log endogenous noradrenaline content. 4. After correction of the rates of total MA uptake for the cocaine-resistant distribution of the amine, a saturable component of uptake was obtained for each tissue. This uptake was considered to be neuronal; it was subjected to kinetic analysis. 5. Apparent Km values for the neuronal uptake of MA were very similar in all tissues and did not show any dependence on the tissue level of endogenous noradrenaline (average Km = 1.2 muM). 6. V max values for the neuronal uptake of MA were linearly correlated with the endogenous noradrenaline content of the tissues (r = 0.976; P less than 0.001), the V max for the vas deferens being excluded. When related to the content of endogenous noradrenaline, the V max obtained in the vas deferens was lower than that for all other tissues. 7. The results presented here strongly suggest that the membrane site involved in neuronal amine uptake (operationally characterized by the Km of MA) is likely to be identical in all rat tissues and that the number of uptake sites available per nerve terminal does not vary greatly between tissues.

Animals↗
PubMed1977

Distribution of metaraminol and its relation to norepinephrine.

A modified fluorometric procedure of high specificity and sensitivity id described for the analysis of metaraminol (MET) in biological material. With this method the distribution of MET was studied in the rat. Except for brain, peripherally administered MET was well distributed. Organs with a large population of norepinephrine (NE) storage vesicles such as the heart, spleen and adrenal, took up relatively large amounts of MET and retained it longer than those tissues with few vesicles such as the liver, lung and kidney. MET had a longer blood half-life than described for NE in other species. In part, this can be attributed to the lack of metabolism of MET as well as our finding that MET, unlike NE, was concentrated in the cellular fraction of blood. Under the conditions of these experiments there was no close correlation on a concentration or time basis with respect to the appearance and disappearance of MET and NE in various organs. This was particularly evident in the adrenal gland where MET resembled reserpine in that one unit of drug displaced many units of catecholamines. In this case, however, we did not rule out a possible contributing effect via the CNS.

Animals↗
PubMed1990

Post-traumatic priapism treated with metaraminol bitartrate: case report.

A 30-year-old male with post-traumatic priapism for 7 days was treated successfully by metaraminol bitartrate injection into the corpus cavernosum. This result suggests that an alpha-adrenagic agent injection into the corpus cavernosum should be considered in post-traumatic priapism at first.

Adult↗
PubMed1969

Regulation of metaraminol efflux from rat heart and salivary gland.

1. The turnover rate of noradrenaline (NA) in heart and submaxillary salivary gland was studied in rats exposed to 4 degrees C or maintained at room temperature (22 degrees C). Cold exposure increased the turnover of the NA store in heart but not in salivary gland.2. In another series of experiments the decline of metaraminol (M) from heart and submaxillary salivary gland was studied in rats exposed to 4 degrees C or maintained at room temperature. Cold exposure accelerated the efflux of M from heart, but not from salivary gland. It is concluded that the accelerated decline of M from heart is the consequence of selective activation of the sympathetic nerves that innervate the heart.3. The turnover of NA was studied in rat heart after the administration of M (100 mug/kg intravenously) or its precursor alpha-methyl-meta-tyrosine (200 mg/kg intraperitoneally). Turnover remained essentially normal after these drugs.4. The administration of desipramine (DMI, 20 mg/kg intraperitoneally) 1 hr after M (100 mug/kg intravenously) induced a rapid sustained efflux of M from heart and salivary gland. The results of this study suggest that the slow decline of M from heart is the result of the great affinity of the amine retrieval mechanism in sympathetic nerve endings for M. DMI inhibits the retrieval mechanism, thus accelerating the efflux of M.

Animals↗