Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review seeks to discuss the possible importance of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in terminating the effects of released sympathetic transmitters and in the inactivation of endogenous or administered sympathomimetic amines with particular reference to some aspects of the cardiovascular system. Use of in vitro preparations of blood vessels and of other smooth muscles, such as vas deferens and anococcygeus, has thrown light on possible roles for these deaminating enzymes, even in the inactivation of noradrenaline, while the new reversible inhibitors of MAO-A show promise as antidepressants with a reduced risk of hypertensive crises following the ingestion of tyramine-containing food. However, the role of SSAO in the in inactivation of amines remains an enigma, even though much is now known of its biochemical nature. While the pharmacological responses to amine substrates can be potentiated by inhibition of SSAO, there is a suspicion that it is product rather than substrate that is more important.
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PMID:Some aspects of the enzymic inactivation of sympathomimetic amines. 311 19

The absence of initiation of "cheese effect" (potentiation of sympathomimetic action of tyramine) by 1-deprenyl (selective monoamine oxidase, MAO-B inhibitor) was regarded to be an intrinsic property of this inhibitor. However, availability of other selective MAO-B inhibitors have clearly shown that this is not the case, since the "cheese effect" is associated with the selective inhibition of MAO-A, the enzyme responsible for intraneuronal oxidation of noradrenaline. Following inhibition of neuronal MAO-A, noradrenaline in the cytoplasmic intraneuronal pool can increase to high levels. Since tyramine releases noradrenaline into the cytoplasm and not by exocytosis, its action is potentiated by inhibition of neuronal MAO-A.
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PMID:Monoamine oxidase B inhibition and the "cheese effect". 348 Sep 39

Recent studies have provided almost conclusive evidence for the existence of the two separate MAO isozymes previously postulated to exist on the basis of indirect evidence. Important differences in the proportions and distribution of these two enzyme forms across species and in various tissues are responsible for some puzzling anomalies in earlier studies and contribute to differences in behavioral responses, blood pressure changes, and toxic responses to tyramine and other sympathomimetic agents. Substrate-selective, irreversible inhibitors, as well as several new classes of reversible MAO-A and MAO-B selective inhibitors, may provide a spectrum of clinical effects different from the nonselective irreversible MAO inhibitors.
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PMID:New contributions from basic science to understanding the effects of monoamine oxidase inhibiting antidepressants. 673 94

The enhanced sensitivity to the pressor effects of tyramine, an indirect-aging sympathomimetic found abundantly in the diet, is a well-known potentially dangerous side effect occurring during treatment with commonly used non-selective monoamine oxidase (MAO) inhibitors. The effects of treatment with the selective MAO-A inhibitor clorgyline and the partially selective MAO-B inhibitors pargyline and deprenyl on tyramine's pressor effects were studied in depressed patients using an IV steady-state tyramine infusion technique. After 4 weeks of treatment, clorgyline produced a significantly greater increase in tyramine sensitivity in comparison to a medication-free baseline (29-fold) than did pargyline (12-fold) or deprenyl (1.7-fold). The pressor effects of tyramine were significantly prolonged after cessation of infusion during both clorgyline and pargyline, but not deprenyl treatment. These data from IV tyramine administrations suggest that intestinal MAO inhibition is not the major determinant of the enhanced tyramine pressor sensitivity produced by clorgyline and pargyline.
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PMID:Tyramine infusions and selective monoamine oxidase inhibitor treatment. I. Changes in pressor sensitivity. 679 Dec 2

MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride] was designed to be a selective, mechanism-based irreversible inhibitor of monoamine oxidase type B (MAO-B). The compound is a potent, selective MAO-B inhibitor in vitro and in vivo. In vitro studies revealed an IC50 value (MAO-B) of 3.6 nM with 189-fold selectivity compared to MAO-A. In rats, profound inhibition of MAO-B was achieved after a single oral dose with an ED50 of 0.18 mg/kg; a dose 44 times this amount was required to inhibit MAO-A by 50%. Selectivity was maintained following chronic dosing. MDL 72,974A had minimal sympathomimetic effects and did not potentiate the cardiovascular effects of tyramine, even at 50 times the MAO-B inhibiting dose. This inhibitor was equally effective and well-tolerated in man. In human volunteers, potent inhibition of platelet MAO-B activity was observed at submilligram doses (ED50 = 90 micrograms) following a single oral dose. Upon multiple oral doses of 100 micrograms, as much as 80% of MAO-B could be inhibited. In phase II studies, MDL 72,974A is proving to be a useful adjunct to conventional therapy. Patients (250) with Parkinson's disease, treated once daily with either 1 or 4 mg, together with L-Dopa and a decarboxylase inhibitor (MadoparR or SinemetR), saw significant improvements in symptoms compared with those on standard therapy without the inhibitor.
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PMID:MDL 72,974A: a selective MAO-B inhibitor with potential for treatment of Parkinson's disease. 829 96

Severe side effects such as hepatotoxicity and potentiation of the sympathomimetic action of tyramine ("the cheese effect") caused the withdrawal of nonselective irreversible monoamine oxidase (MAO) inhibitors from use in psychiatric therapy. The development of selective irreversible inhibitors for MAO type A did not eliminate cardiovascular side effects such as "the cheese effect" or, conversely, the hypotensive effect of these drugs. To overcome at least "the cheese effect," selective reversible MAO-A inhibitor antidepressants such as moclobemide and brofaromine have been developed. Being reversibly bound to MAO, these drugs may be displaced from their binding site in the intestine by ingested, indirectly sympathomimetic amines such as tyramine, thus avoiding the initiation of the hypertensive crises. Using a rat renal nerve preparation, we have demonstrated that acute administration of either moclobemide or brofaromine (10 mg/kg) does not cause a decrease in blood pressure or a significant reduction in sympathetic renal nerve activity. These data contrast with those obtained with clorgyline or desipramine. The results indicate that moclobemide and brofaromine may be devoid of a hypotensive effect, including orthostatic hypotension.
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PMID:The advent of a new generation of monoamine oxidase inhibitor antidepressants: pharmacologic studies with moclobemide and brofaromine. 831 92

The "cheese effect", potentiation of sympathomimetic action of indirectly acting amines such as tyramine, the main side effect of irreversible non-selective and selective monoamine oxidase (MAO) A inhibitors, has largely been eliminated in the new generation of reversible selective MAO-A and B and irreversible MAO-B inhibitors. These selective inhibitors are demonstrating unique pharmacology and initial controlled clinical studies are providing evidence to support their action as anti-depressants and anti-Parkinson's disease drugs and possibly as neuroprotectors. Thirty years of experience with non-selective MAO inhibitors has resulted in a better understanding and management of the new generation of MAO inhibitors. Because of their selective action on the specific forms of MAO, which results in selective elevation of brain noradrenaline and serotonin on the one hand and dopamine and phenylethylamine on the other, it is hoped that these drugs will be able to elucidate the functional roles of MAO-A and B subtypes with regards to dopamine metabolism in the human brain.
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PMID:Dopamine metabolism and neurotransmission in primate brain in relationship to monoamine oxidase A and B inhibition. 839 Feb 70

After initial enthusiasm, the use of monoamine oxidase inhibitors (MAOIs) has been limited by the wide range of MAOI-drug and MAOI-food interactions that are possible, particularly with sympathomimetic medications or tyramine-containing foods, resulting in hypertensive reactions. Despite their clinical benefits, this has led to a reduction in use of such medications. Discovery of the 2 main subgroups of monoamine oxidase, types A and B, led to the synthesis of MAOIs selective for one or other of these isoenzymes. Consequently, selegiline (deprenyl), a selective MAO-B inhibitor, was developed for the treatment of idiopathic Parkinson's disease. This drug is useful in the treatment of the early stages of the disease and later on as an adjunct to other drug therapies. Although the selective MAO-A inhibitor, clorgiline (clorgyline), was found to be effective in the treatment of depression, it still retained the potential to cause hypertensive reactions. Recently, agents that are not only selective, but reversible in their inhibition of MAO-A (RIMAs) have been synthesised (e.g. moclobemide and toloxatone), and have proven antidepressant efficacy. Whilst they are less likely to induce hypertensive reactions with the concomitant administration of sympathomimetic drugs or with tyramine-rich foodstuffs, it still seems wise to advocate care in co-prescribing potentially interacting medications and to advise a degree of caution with regard to the dietary intake of foodstuffs likely to contain a high tyramine content. Although these newer drugs represent an advance in safety, their use has, as yet, only been established in the treatment of depression. RIMAs also retain a potential for adverse interaction with other drugs. Concomitant prescription of serotonin-enhancing drugs should only be undertaken with caution for patients on moclobemide, toloxatone or selegiline. Coprescription of sympathomimetic drugs should also be avoided with these newer MAOIs and patients should be advised against purchasing over-the-counter preparations that may contain sympathomimetic drugs.
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PMID:Monoamine oxidase inhibitors. An update on drug interactions. 871 90

Irreversible, nonselective monoamine oxidase (MAO) inhibitors have been reported adversely to interact with indirectly acting sympathomimetic amines present in many cough and cold medicines. This study investigated the safety and tolerability of concomitant administration to 12 healthy subjects of both genders (aged 19-36 years) of ephedrine and moclobemide, a reversible MAO-A inhibitor. A 2-day, randomized, crossover administration of placebo or ephedrine (two doses of 50 mg with a 4-h interval) was followed by 9 days open-label dosing with moclobemide, 300 mg b.i.d.. On the last 2 days of moclobemide dosing, the randomized crossover treatment of ephedrine and placebo was repeated. No subject was withdrawn from the study for tolerability reasons. Moclobemide treatment, however, increased the incidence of adverse events elicited by ephedrine, particularly palpitations and headache. The pharmacodynamic interaction between the two drugs was quantified by calculation of the area under the effect-time course (AUE) for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR). The difference in AUE between monotreatment with ephedrine and placebo was statistically significant for all three vital signs. Moclobemide potentiated the effect of ephedrine by a median factor of 3.2 for SBP, 3.8 for DBP, and 0.6 for HR. Ephedrine had no significant influence on the plasma concentrations of moclobemide or its metabolites. In conclusion, the combined use of moclobemide and high doses of sympathomimetic drugs should be approached with caution.
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PMID:Modification of the cardiovascular effects of ephedrine by the reversible monoamine oxidase A-inhibitor moclobemide. 896 Oct 85

We report a case of low thoracic epidural and general anaesthesia in a patient receiving moclobemide, a new selective inhibitor of monoamine oxidase A. Intra-operative hypotension was initially treated with phenylephrine and then with ephedrine. The short half-life of moclobemide and its modest interaction with direct and indirect acting sympathomimetic drugs permit the use of epidural anaesthesia, since any associated hypotension can be safely treated.
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PMID:Epidural anaesthesia, ephedrine and phenylephrine in a patient taking moclobemide, a new monoamine oxidase inhibitor. 903 53


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