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PubMed1989

The pharmacology of reversible monoamine oxidase inhibitors.

The older monoamine oxidase inhibitors (MAOIs) are mechanism-based, irreversible inhibitors of MAO; most inhibit both the A and B forms of MAO. Several of the drugs are hydrazine derivatives which have non-specific effects other than MAO inhibition. These properties convey disadvantages, which may be seen as serious, though infrequent, adverse events--the 'cheese effect', hepatotoxicity, amphetamine-like activity, orthostatic hypotension and anticholinergic effects. New, reversible MAOIs stem from a variety of chemical classes and are more specific in their effects, with relatively rapid onset of action, direct relationship between plasma concentration and pharmacological effect, and no prolonged carry-over phenomena.

Administration, Oral↗
PubMed1996

Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets.

Traditional monoamine oxidase inhibitors (MAOIs) remain an important class of drugs for a variety of psychiatric conditions, including depressive illnesses, anxiety, and eating disorders. It was the objective of this study to refine the MAOI diet by determining the tyramine content of a variety of untested and "controversial" foods that continue to appear on MAOI diet-restricted food lists. A secondary objective of the study was to evaluate the effect of freshness on the tyramine content of some foods. Fifty-one food samples were evaluated for tyramine content by liquid chromatography. Food samples included a selection of sausages, beverages, sliced meat products, including chicken liver, and some fruits, including raspberries, bananas, and banana peels. Foods that were found to have dangerously high concentrations of tyramine (> or = 6 mg/serving) included chicken liver aged 9 days (63.84 mg/30 g), air-dried sausage (7.56 g/30 g), soy sauce (0.941 mg/ml), and sauerkraut (7.75 mg/250 g). Of the foods analyzed in this study, only those with high tyramine content per serving should continue to be absolutely restricted. All other foods are either safe for consumption or safe in moderation. The data provided should be combined with the data from other similar analytical studies to develop a list of foods that should be absolutely restricted. A more accurate list of restricted foods may enhance patient dietary compliance.

Diet Therapy↗
PubMed1985

Serotoninergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors.

Repeated administration of monoamine oxidase inhibitors induces a transient decrease in the firing rate of serotoninergic neurons followed by complete recovery, whereas it results in a persistent reduction of the firing rate of noradrenergic neurons. Under these conditions, serotoninergic, but not noradrenergic, neurons undergo a desensitization of their somatic autoreceptors. Serotoninergic neurons therefore show the capacity to free themselves from their autoregulatory control, a property which noradrenergic neurons appear to be lacking. The time course of the recovery in the firing rate of the serotoninergic neurons is consistent with the delayed antidepressant effect of monoamine oxidase inhibitors.

Animals↗
PubMed1980

Correlation between monoamine oxidase inhibitors and anticonvulsants.

Monoamine oxidase inhibitory and anticonvulsant properties of 2-substituted styryl-6-bromo-3-(4-ethylbenzoate/4 benzhydrazide)-4-quinazoles are studied. All styryl quinazolone esters except compound number 9 exhibited monoamine oxidase inhibitory properties during oxidative deamination of kynuramine. Corresponding hydrazides were found to have relatively higher activity. All these quinazolones were able to protect against pentylenetetrazol induced seizures. These observations in general do not prove that monoamine oxidase inhibitory properties represent the biochemical basis for the anticonvulsant activity of these compounds.

Animals↗
PubMed2006

Effects of monoamine oxidase inhibitors on cocaine discrimination in rats.

This study tested the time course of the discriminative stimulus effects of inhibitors of monoamine oxidase alone or in combination with cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg, intraperitoneal) from saline using a two-lever choice methodology. The nonselective monoamine oxidase inhibitors tranylcypromine (0.01-5 mg/kg) and phenelzine (1-25 mg/kg), the monoamine oxidase-A selective compound clorgyline (1-25 mg/kg), and the monoamine oxidase-B selective compounds pargyline (0.005-50 mg/kg) and selegiline (1-25 mg/kg) were tested for substitution 15 min or 24 h following administration, and in combination with 10 mg/kg of cocaine 24 and 48 h after administration. At 15 min, selegiline fully substituted for the discriminative stimulus effects of cocaine, whereas all other compounds partially substituted. At 24 h, substitution of cocaine was diminished for all compounds except phenelzine, which produced a greater amount of substitution at 24 h than at 15 min. When cocaine was administered 24 h after clorgyline, selegiline, pargyline, and phenelzine, cocaine-appropriate responding was attenuated at intermediate doses of these drugs, whereas the highest doses did not alter cocaine-lever responding. All compounds except selegiline substantially decreased response rate and produced various adverse effects. At 48 h, the effects of all compounds except phenelzine were markedly reduced. Selectivity for monoamine oxidase-A or monoamine oxidase-B did not predict the ability to substitute for or attenuate the subjective effects of cocaine. These findings suggest that monoamine oxidase inhibitors can modulate the discriminative stimulus effects of cocaine for at least 24 h, and may be useful for treatment of cocaine abuse.

Animals↗
PubMed2002

Monoamine oxidase inhibitors: a new generation.

Monoamine oxidase inhibitors (MAOIs), which ushered in the modern era of psychopharmacology in the 1950s, have remained useful in the treatment of depression despite important safety concerns, such as acute hypertensive episodes brought on by ingestion of foods with high-tyramine content. Experience has shown that MAOIs are broadly effective in the treatment of depressive disorders, including atypical, chronic, and double depressions. Newer selective and reversible inhibitors of the two forms of mitochondrial monoamine oxidase (MAO) enzymes, MAO-A and MAO-B, have been developed in an effort to improve the safety and tolerability of MAOIs. Selegiline, a selective inhibitor of MAO-B has been shown to be effective in the treatment of depression at higher oral doses where selectivity for MAO-B is lost. Transdermal delivery of selegiline bypasses first-pass metabolism and avoids impairment of the gastrointestinal barrier provided by MAO-A of the gastrointestinal mucosa. Studies have shown that the selegiline transdermal system (STS) does not significantly affect sensitivity to ingested tyramine, unlike tranylcypromine, which markedly increases sensitivity. STS has been found to be efficacious in the treatment of patients with major depression in placebo-controlled trials, without the need for dietary precautions. The favorable safety profile of STS should allow this MAOI to be a broadly used antidepressant drug.

Administration, Cutaneous↗
PubMed1996

[Monoamine oxidase inhibitors in psychiatry. Status of current knowledge].

With the introduction of moclobemide as the first reversible and selective inhibitor of monoamine oxidase (type A), the therapeutic principle of monoamine oxidase inhibition gained new importance. In this paper the clinical pharmacology, efficacy and side effects of traditional monoamine oxidase inhibitors and specifically of tranylcypromine as an example) are compared with those of the reversible and selective monoamine oxidase inhibitors (as exemplified by moclobemide).

Antidepressive Agents↗
PubMed1959

Alterations in the pattern of amine excretion in man produced by a monoamine oxidase inhibitor.

The administration of monoamine oxidase inhibitors produces an increase in the urinary excretion of many amines for which efficient alternate routes of metabolism are not available. These include tryptamine, paratyramine, and a "metatyramine-like" substance. The inhibitors can therefore be used to detect previously unsuspected pathways of amino acid decarboxylation. The finding that the excretions of norepinephrine, epinephrine, 3,4-dihydroxyphenylethylamine, and possible serotonin are not appreciably affected are consistent with previous reports of the existence of alternative metabolic routes.

Amines↗
PubMed1989

Monoamine oxidase, monoamine oxidase inhibitors, and panic disorder.

Monoamine oxidase inhibitors are effective in the treatment of panic attacks. Phenelzine has been used most often with good effect and is regarded by some as the treatment of first choice for panic disorders. Nevertheless the potential dangers of the use of non-specific MAOIs are well recognised and there is a need for safer drugs. The efficacy of specific MAO inhibitors such as moclobemide (MAO-A) and deprenyl (MAO-B) are yet to be investigated. The activity of the enzyme MAO in blood platelet (MAO-B) has been extensively studied. A review of early findings of elevated MAO activity suggests a number of reasons why the data should be interpreted with caution. Recent studies do not support the earlier findings and suggest no difference in platelet MAO activity between patients and controls. Similarly studies of the endogenous MAO inhibitor, tribulin, suggest that the output in panic disorder patients is similar to that of controls. Studies of the effectiveness of specific MAOIs in panic attacks are warranted as are further studies of the biochemical aetiology.

Fear↗
PubMed1985

Unit activity in the dorsal raphe in freely-moving cats. Effect of monoamine oxidase inhibitors.

Two commonly used monoamine oxidase inhibitors, tranylcypromine and pargyline, produced dose-dependent decreases in the activity of serotonin-containing neurons in the dorsal raphe in awake, freely-moving cats. The onset of the suppression of unit activity occurred within 15-20 min after administration of drug and persisted for 6-16 hr, depending upon dose. Parallel neurochemical studies revealed that serotonin in the brain was significantly increased following inhibition of monoamine oxidase, and that concentrations of serotonin were still significantly elevated after unit activity in the raphe had returned to baseline levels. These data suggest that autoreceptors on neurons of the dorsal raphe may become tolerant following prolonged exposure to large concentrations of serotonin.

Animals↗
PubMedDate not supplied

Monoamine oxidase inhibitors and elective surgery.

Monoamine oxidase inhibitor use is considered a contraindication for elective surgery. We reviewed 32 patients on a regimen of isocarboxazid 10 mg daily who underwent elective surgery. Their anesthetic management, postanesthesia outcome, and pharmacology are described.

Adult↗
PubMed1988

Monoamine oxidase inhibitors in anxiety disorders.

Monoamine oxidase inhibitors (MAOI's) have been shown to be significantly superior to placebo in the treatment of some anxiety disorders, particularly agoraphobia and mixed anxiety--depressive states. There is no convincing evidence that MAOI's are effective treatment in pure anxiety states, whether or not panic is present as a major symptom, although they are effective in so-called endogenous anxiety. Many past published studies of MAOI's have yielded poor results because the drugs have been prescribed for insufficient time (less than four weeks) or at too low dosage. There are no important therapeutic differences between the MAOI's apart from the faster speed of response with the nonhydrazine compound, tranylcypromine. Treatment often has to be long-term, and some degree of pharmacological dependence may develop. A few clinical studies have compared the efficacy of MAOI's and tricyclic antidepressants in anxious disorders. There is growing evidence that MAOI's are somewhat more effective than tricyclic antidepressants in the treatment of anxiety disorders and when phobic anxiety is an important component of a depressive disorder.

Antidepressive Agents, Tricyclic↗
PubMed1985

The present status of monoamine oxidase inhibitors.

The present status of monoamine oxidase inhibitors in the treatment of depression is reviewed. With adequate doses they are effective antidepressants, but dosages have in the past been too low. Provided proper dietary precautions are taken, the incidence of fatality from dietary interactions is very small and should not deter doctors from using these drugs, especially in those depressed patients who do not respond to tricyclic-type antidepressants. The present status of combining monoamine oxidase inhibitors with tricyclics is discussed, as are the newer specific inhibitors particularly clorgyline and deprenyl.

Acetylation↗
PubMed1985

Treatment of hyperactive children with monoamine oxidase inhibitors. II. Plasma and urinary monoamine findings after treatment.

Urinary monoamines and metabolites as well as plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol were measured in 14 boys (mean age, 9.2 years) with Attention Deficit Disorder With Hyperactivity during an initial placebo period, after four weeks of treatment with either dextroamphetamine sulfate (N=5) or a monoamine oxidase inhibitor (N=9) and at the end of a subsequent two-week placebo "washout" period. Both dextroamphetamine and monoamine oxidase inhibitors produced persistent changes in monoamines and metabolites, which were most marked and consistent for NE and its metabolite 3-methoxy-4-hydroxyphenylglycol. These changes did not correlate in a consistent fashion with clinical response during drug treatment. Moreover, there was rapid clinical relapse following cessation of either treatment while the alterations in NE metabolism remained during the two weeks following drug, further demonstrating the independence of these changes from clinical state. Future studies with dextroamphetamine need drug-free periods that are greater than 14 days to obtain true "baseline" conditions.

Amines↗