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PubMed1980

Lymphocyte monoamine oxidase activity and chronic schizophrenia.

Lymphocyte monoamine oxidase (MAO) activity was assayed in 62 chronic schizophrenic patients, 113 normal volunteers, and 23 first-degree relatives of schizophrenic patients. Mean lymphocyte MAO activity was significantly lower (p < 0.001) in the chronic schizophrenic group than in controls; first-degree relatives had a mean lymphocyte MAO activity midway between the schizophrenics and normals. No relationship was found between lymphocyte MAO activity and sex or age of subjects. When subjects were subgrouped by race, blacks had significantly lower MAO activity than whites (p < 0.001).

Adolescent↗

PubMed1977

Low platelet monoamine oxidase activity in human alcoholics.

Platelet monoamine oxidase (MAO) activity was found to be significantly reduced in human alcoholics as compared to matched controls. A probable transitory increase in activity was observed during the abstinence phase. The low platelet MAO activity was not due to iron deficiency or to the presence of acetaldehyde. Since we have previously found a lowered MAO activity in the brains of suicide victims, especially in those with a previous history of alcohol abuse, we suggest that low platelet MAO activity reflects a primarily "weak" monoaminergic system in the CNS which causes an increased vulnerability to alcohol abuse and suicidal behaviour.

Alcoholism↗

PubMed1980

Platelet monoamine oxidase activity in megaloblastic anaemia.

Platelet monoamine oxidase activity has been measured in 17 patients with megaloblastic anaemia due to either vitamin B12 or folate deficiency, and in 20 healthy subjects. There was a highly significant increase in patients compared with controls. In two patients, platelet activity decreased following successful treatment. A significant correlation between platelet activity and the severity of bone marrow megaloblastic change, assessed by the deoxyuridine suppression test and bone marrow morphology, was also observed. If the change in activity also occurs in the nervous system, this may contribute to the mental disturbance associated with vitamin B12 or folate deficiency.

Anemia, Macrocytic↗

PubMed1983

An inverse correlation between spontaneous eye-blink rate and platelet monoamine oxidase activity.

An inverse correlation between platelet monoamine oxidase activity and spontaneous eye-blink rate, a putative measure of central dopaminergic activity, was found in medication-free chronic schizophrenic patients without tardive dyskinesia (n = 20, rs = -.47, P less than .025). A similar correlation was found when patients with tardive dyskinesia were included but was weaker (n = 27, rs = -.35, P less than .05). Normal controls and patients with tardive dyskinesia did not demonstrate this relationship. This report confirms a previous finding of a significant platelet monoamine oxidase-blink rate correlation in chronic schizophrenic patients. Insofar as this relationship is mediated by dopamine, it suggests that dopaminergic relations are more readily demonstrated in schizophrenic subjects than normals. Moreover, tardive dyskinesia appears to obscure this dopaminergic relationship.

Adult↗

PubMed1982

A commingling analysis of platelet monoamine oxidase activity.

The distribution of platelet monoamine oxidase (MAO) activity is examined in a large cohort of 18-year-olds from a college setting. A mixture of three distributions is needed to describe the data, even when a power transformation is used to remove skewness in the distribution. This is compatible with MAO activity being controlled by a single major locus with a gene frequency of 0.02 for high-MAO activity. Accordingly, it is unlikely that such a locus could serve as a genetic marker for a disorder which is associated with low activity. However, this finding does not rule out the possibility that MAO activity is an associated risk factor in disease.

Adult↗

PubMed1985

Chlorphentermine inhibits pulmonary mitochondrial monoamine oxidase.

Oxidation of six amine substrates by rat, rabbit and guinea-pig lung mitochondrial monoamine oxidase (MAO) was investigated polarographically with a Clark oxygen electrode in the presence of chlorphentermine (CP). This amphiphilic drug decreased the deamination of serotonin, norepinephrine, tyramine and dopamine significantly in all three species. However, the oxidation of tryptamine and benzylamine was unchanged. Amine oxidation by MAO in guinea-pig lung mitochondria was much more sensitive to the CP-mediated inhibition than rat or rabbit. A kinetic study of serotonin oxidation in the absence and presence of CP showed that both Vmax and Km were affected. These combined data indicate that CP is a specific inhibitor of pulmonary, mitochondrial monoamine oxidase form A with mixed-type inhibition.

Animals↗

PubMed2001

Oxygen dependency of monoamine oxidase activity in the intact lung.

Hydrogen peroxide generated by monoamine oxidase (MAO)-mediated deamination of biogenic amines has been implicated in cell signaling and oxidative injury. Because the pulmonary endothelium is a site of metabolism of monoamines present in the venous return, this brings into question a role for MAO in hyperoxic lung injury. The objective of this study was to evaluate the O(2) dependency of the MAO reaction in the lung. To this end, we measured the pulmonary venous effluent concentrations of the MAO substrate [(14)C]phenylethylamine and its metabolite [(14)C]phenylacetic acid after the bolus injection of either phenylethylamine or phenylacetic acid into the pulmonary artery of perfused rabbit lungs over a range of PO(2) values from 16 to 518 Torr. The apparent Michaelis constant for O(2) was approximately 18 microM, which is more than an order of magnitude less that measured for purified MAO. The results suggest a minimal influence of high O(2) on MAO activity in the normal lung and demonstrate the importance of measuring reaction kinetics in the intact organ.

Animals↗

PubMed1977

Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy.

Combinations of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are discussed with regard to general toxicity, drug interactions, animal studies, clinical reports, efficacy of combination therapy and usage conditions. Although MAOI-TCA combinations are usually considered contraindicated, informed opinion has shifted to cautious recommendation for the combination. Only refractory patients in whom less hazardous treatment has failed should be considered for combination therapy. The preferred dosage regimen is administration of the MAOI t.i.d. during the day and the entire TCA dose at bedtime. Patients should be informed of the immediate need for medical advice should side effects occur. It is concluded that the simultaneous administration of these agents is potentially efficacious and safe is carefully monitored and controlled.

Animals↗

PubMed1988

Molecular cloning of a cDNA for rat liver monoamine oxidase B.

The cDNA for rat monoamine oxidase B mRNA was isolated from liver cDNA library in lambda gt11 using specific antibody and oligonucleotide probes derived from FAD-containing peptide of the enzyme. The primary structure of the protein, deduced from the nucleotide sequence, consisted of 520 amino acid residues and its molecular weight was calculated to be 58.4 kD which is in good agreement with that of the in vitro-synthesized peptide. FAD-binding site is located in the carboxy-terminal region. There is no typical structural feature common to the targeting signals for mitochondria, the periodic distribution of basic amino acids spaced by several uncharged residues, at its amino-terminal region. This region has an uninterrupted stretch of 14 hydrophobic residues.

Amino Acid Sequence↗

PubMed1981

Kinetic aspects of monoamine oxidase activity in twins with psychoses.

Monoamine oxidase activity was assayed in platelets from 22 (8 monozygotic and 14 dizygotic) twin pairs. At least one twin of each pair had a serious psychiatric disorder (proband). Phenethylamine was used as substrate and the assay was performed at two different oxygen concentrations (0.06 and 0.12 nM). Apparent Km and Vmax values were estimated from double reciprocal plots. The correlation between proband and control twins was high for both apparent Km (r = 0.83) and Vmax (r = 0.69) when the enzyme was assayed at the higher concentration of oxygen. The monozygotic twins pairs showed very high correlations (Km r = 0.93; Vmax r = 0.86) as compared to dizygotic twins (Km r = 0.81, Vmax r = 0.50) and apparently healthy subjects (Km r = 0.46, Vmax r = 0.33). No difference in kinetic properties was found between schizophrenic and non-schizophrenic twins.

Blood Platelets↗

PubMed1985

In vivo effect of MPTP on monoamine oxidase activity in mouse striatum.

Striatal monoamine oxidase (MAO)-B, but not MAO-A, activity decreased in mice at 2 and 10 days and was back to control values at 20 and 30 days after systemic administration of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Striatal dopaminergic (DA) depletions were maximal at 2 days and were only partially reversed at 30 days post-treatment. In rats, unilateral kainic acid lesions increased MAO-B but not MAO-A activity probably due to reactive gliosis, but MPTP did not affect DA levels in control and kainic acid-lesioned striata. Findings support the importance of MAO-B in the toxicity of MPTP and suggest that resistance of rat DA neurons to the neurotoxin is probably not due to species differences in MAO-B activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1993

Modulation of capsaicin induced airway reflexes in humans: effect of monoamine oxidase inhibition.

1. In animal studies monoamine oxidase (MAO) inhibition has been shown to reduce the cough response through elevation of 5-HT in the central nervous system. In this study the effect of selective inhibition of the two subtypes of MAO (MAO-A and MAO-B) was studied on human airway reflexes. 2. Capsaicin-induced cough and reflex increase in respiratory resistance were measured in nine normal volunteers before and after MDL 72394 (MAO-A inhibitor) 16 mg or MDL 72974A (MAO-B inhibitor) 12 mg. 3. Neither inhibitor altered capsaicin-induced cough. Following treatment with MDL 72394, however, the capsaicin-induced reflex increase in resistance was enhanced, by 5.97 +/- 2.1 fold of the placebo value at 1 h. 4. Thus, neurotransmitters in the central nervous system which are substrate for MAO-A (i.e. noradrenaline, 5-HT) may be involved in the control of capsaicin-induced reflex bronchoconstriction.

Adult↗

PubMed1997

Tap (draft) beer and monoamine oxidase inhibitor dietary restrictions.

OBJECTIVE: Traditional monoamine oxidase inhibitors (MAOIs) continue to play an important role in the management of a wide variety of clinical conditions. Accordingly, a practical and safe approach to MAOI dietary restrictions remains an essential component of patient management. METHOD: In an effort to refine MAOI dietary recommendations, we report a case of hypertensive crisis following the consumption of a modest amount of tap beer. RESULTS: A well-documented case report involving tap (draft) beer consumed while on an MAOI supports an earlier study, which recommended that all tap beers be restricted on MAOI diets. The 2 cases were remarkably similar in terms of the offending substance, quantity consumed, and subsequent reaction. CONCLUSIONS: As a result of recent tyramine analyses and 2 well-documented case reports, all tap (draft) beers should now be absolutely restricted on MAOI diets because they represent a very significant risk at modest levels of consumption.

Adult↗

PubMed1984

Diet and monoamine oxidase inhibitors: a re-examination.

Monoamine oxidase inhibitors (MAOIs) are attracting renewed attention as effective antidepressants for refractory depressions, particularly among the elderly. However, widespread fears concerning the interactions of MAOIs with tyramine-containing foods have led to the development of long and complicated diets. These diets have served as an obstacle to the ready use of MAOIs, yet very little systematic or critical review of the basis for food restriction has been undertaken. An international survey of MAOI diets was conducted and from the diets collected, foods were categorized according to frequency of restriction on the diet lists. On the basis of this survey and a critical review of the literature it was determined that only four foods clearly warrant absolute prohibition: aged cheese, pickled fish (herring), concentrated yeast extracts and broad bean pods. While there is insufficient evidence to prohibit alcohol completely (even chianti wine) true moderation must apply. It is suggested that a radically simplified diet should be investigated on a prospective basis.

Animals↗

PubMed1995

Switch in treatment from tricyclic antidepressants to moclobemide: a new generation monoamine oxidase inhibitor.

The combination of classic monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressant drugs (TCAs) has been associated with a variety of adverse events. A switch in treatment from TCAs to moclobemide, a reversible and selective inhibitor of MAO-A, was investigated in a double-blind, placebo-controlled study in healthy volunteers. Two groups of 12 subjects were treated with either amitriptyline (75 mg/day) or clomipramine (100 mg/day) until steady-state conditions had been attained (14 days). Treatment with the TCAs was discontinued abruptly and switched to either a therapeutic dose regimen of moclobemide (300 mg/day) or placebo. The tolerability and safety pattern did not reveal any clinically relevant differences between moclobemide and placebo recipients, nor was there any sign of a pharmacokinetic interaction between the TCAs and moclobemide. In conclusion, the findings of this study suggest that therapeutic doses of moclobemide up to 300 mg daily can be given 24 hours after the last dose of treatment with either amitriptyline or clomipramine without major risks.

Adolescent↗

PubMed1994

Pharmacological actions of l-deprenyl (selegiline) and other selective monoamine oxidase B inhibitors.

The acetylenic selective monoamine oxidase (MAO) type B suicide inhibitor, l-deprenyl (l-selegiline), has proved to be a useful adjuvant to L-dopa therapy and monotherapy of Parkinson's disease. Although not all features of its antiParkinson action are known, studies that used brains obtained at autopsy from patients who took l-deprenyl show that the selective inhibition of MAO-B with a concomitant increase of phenylethylamine and dopamine, but not of serotonin or noradrenaline, in the basal ganglia may be responsible for its mode of action. The increased life expectancy noted in patients with Parkinson's disease who received long-term therapy (9 years in an uncontrolled study) is another unexpected feature of the drug. These exciting data, if confirmed in other long-term clinical trials, may herald a neuroprotective approach to the treatment of this degenerative disease. More recent studies indicate that Parkinson's disease may eventually turn out to be a neurotoxic event resulting from oxidative stress-induced free radical species in the substantia nigra. Thus selective MAO-B inhibitors could represent a unique class of drugs, having symptomatic actions with possible neuroprotective and neurorescue actions in one.

Animals↗

PubMed2003

Molecular cloning of canine monoamine oxidase subtypes A (MAOA) and B (MAOB) cDNAs and their expression in the brain.

The role of monoamine oxidase has been shown to be related to some behavioral changes including aggression and cognitive dysfunction. In order to demonstrate the basic expression patterns of monoamine oxidase in the canine brain, we determined the full-length nucleotide sequences of cDNA for canine monoamine oxidase type A (MAOA) and type B (MAOB) genes that were isolated from the canine brain cDNA library. Oligonucleotide primers for PCR were constructed based on the conserved sequences reported thus far for other mammalian species. The nucleotide sequences had open reading frames of 1584 and 1563 bp for MAOA and MAOB, respectively. Both of these genes showed relatively high homology with other species in both nucleotide (> 81%) and deduced amino acid (> 85%) sequences. In Northern blot analyses MAOA mRNA was expressed broadly in various parts of the canine brain, whereas MAOB mRNA was found only in specific brain regions, such as the hypothalamus, hippocampus, brain stem and olfactory bulb. These results suggest that MAOA and MAOB mRNAs have subtype-specific expression patterns in the canine brain.

Amino Acid Sequence↗

PubMed1980

The effect of age on the activity and molecular properties of human brain monoamine oxidase.

The effect of age upon monoamine oxidase -A and -B (MAO-A and -B) in 23 different, regions of human brain was determined. There was a significant positive correlation with age in 19 out of 23 regions for MAO-B, but no positive correlation with age was found for MAO-A. The increased MAO-B activity was found, in 5 out of 5 regions tested, to be due entirely to an increased enzyme concentration, rather than due to an increased molecular turnover number of the enzyme. The responses of the mitochondrial marker enzymes succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were studied in 5 brain regions, and no consistent change in activity found with age. The lysosomal enzyme acid phosphatase was found to tend towards an increased activity with age. No difference in either the specific activities or molecular characteristics of MAO were found between men and women. Cross-correlation studies of the data, after compensation for the effects of age, indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain. Such a finding is consistent with a genetic regulation of the enzyme forms.

Adult↗