Showing papers on "Monoamine oxidase B published in 1976"
197 citations
TL;DR: The α-methyl-substituted amines dl-α-methylbenzylamine, d- α-methyltryptamine and the two stereoisomers of amphetamine were shown to be competitive inhibitors of the oxidation of benzylamines, tyramine and serotonin by rat liver monoamine oxidase.
170 citations
TL;DR: The results suggest that the deamination of dopamine in vivo is almost entirely effected by MAO A, and that clorgyline potentiated the effect of l-DOPA on motor activity; deprenil did not.
Abstract: The effect of graded doses of clorgyline, a preferential inhibitor of MAO A, and of deprenil, a preferential inhibitor of MAO B, on the activities of serotonin-deaminating MAO (MAO A) of dopamine-deaminating MAO, and of phenethylamine-deaminating MAO, (MAO B), in rat corpus striatum were compared with the effects of the drugs on striatal levels of homovanillic acid(HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). The dose-response curves for the two last-mentioned dopamine metabolites closely follow those for MAO A and dopamine-deaminating activity, whether clorgyline or deprenil was used as MAO inhibitor. In addition, the effect of these drugs on dopamine levels and on the accumulation of 3H-dopamine + 3H-methoxytyramine formed from 3H-DOPA in rat whole brain was analysed. In contrast to the marked increases caused by clorgyline, the effects of deprenil were negligible. In reserpinized rats, clorgyline potentiated the effect of L-DOPA on motor activity; deprenil did not. These results suggest that the deamination of dopamine in vivo is almost entirely effected by MAO A.
131 citations
TL;DR: Two activities of membrane-bound monoamine oxidase (MAO) can be distinguished in mammalian tissues with the aid of substrate selective inhibitors and the problem of selectively inactivating one of the two forms during purification is well known.
81 citations
TL;DR: It is concluded that the short-term control of catecholamine synthesis presumably involves two independent feedback mechanisms, one intraneuronal mechanism operating via end-product inhibition, and one synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively.
Abstract: The influence of varying brain levels of dopamine, noradrenaline and 5-HT on their respective synthesis rates has been investigated. The first step in monoamine synthesis was studiedin vivo by measuring the accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic L-amino acid decarboxylase. Variations in monoamine levels were obtained by combined treatment with inhibitors of the decarboxylase (NSD 1015 or Ro 4-4602) and of monoamine oxidase (pargyline). An increase in monoamine levels by pargyline was found to inhibit the synthesis of dopamine, noradrenaline and 5-HT. Conversely, a decrease in monoamine levels induced by the decarboxylase inhibitor Ro 4-4602 appeared to stimulate dopamine and noradrenaline synthesis but had no effect on 5-HT synthesis. The influence of varying levels of dopamine and noradrenaline on the synthesis of these amines could still be demonstrated after blockade of dopamine receptors and ofα-adrenergic (noradrenaline) receptors by haloperidol, suggesting that the mechanism involved in this feedback control is mediated via end-product inhibition of tyrosine hydroxylase. On the other hand, the stimulating influence of haloperidol on the synthesis of catecholamines does not seem to be directly related to changes in catecholamine levels. It is concluded that the short-term control of catecholamine synthesis presumably involves two independent feedback mechanisms, one intraneuronal mechanism operating via end-product inhibition, and one synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively. Both pre- and postsynaptic receptors may be involved in the latter mechanism.
70 citations
TL;DR: The biogenic amines norepinephrine, dopamine and serotonin have been shown to be highly localized in specific neurones within the mammalian brain s,29 and evidence is added to the hypothesis that each amine must play a different role in the central nervous system.
63 citations
TL;DR: All additional substrates investigated were able to inhibit the activity towards β-phenylethylamine in a competitive fashion, indicating that the ‘B form’ of monoamine oxidase appears to be able to oxidize this substrate.
57 citations
TL;DR: The authors emphasize the importance of simultaneous processing of control and patient blood samples and the use of carefully controlled techniques, since relatively minor changes in procedure can markedly influence platelet yield and leucocyte contamination.
Abstract: The activity of platelet monoamine oxidase in 12 chronic schizophrenic patients was not significantly different from that in a matched group of normal individuals. The authors emphasize the importance of simultaneous processing of control and patient blood samples and the use of carefully controlled techniques, since relatively minor changes in procedure can markedly influence platelet yield and leucocyte contamination.
55 citations
TL;DR: Monoamine oxidase has decreased activity in noradrenergic murine neuroblastoma cell lines lacking hypoxanthine phosphoribosyltransferase activity and in skin fibroblasts from patients with the Lesch-Nyhan syndrome.
Abstract: The Lesch-Nyhan syndrome in humans is characterized by lack of hypoxanthine phosphoribosyltransferase activity and neurologic abnormalities that suggest changes in catecholamine metabolism. Monoamine oxidase, which degrades biogenic amines, has decreased activity in noradrenergic murine neuroblastoma cell lines lacking hypoxanthine phosphoribosyltransferase activity and in skin fibroblasts from patients with the Lesch-Nyhan syndrome.
55 citations
TL;DR: It is suggested that C6 glial cells contain mainly monoamine oxidase type A, which previously had been suggested to be primarily an intraneuronal MAO type, which helps explain why MA0 activity measured with some substrates may be little affected by lesions or by drugs producing nerve ending degeneration.
Abstract: Cultured C6 rat glial cells preferentially deaminated 5-hydroxytryptamine, tryptamine, dopamine and tyramine in comparison to phenylethylamine and benzylamine. Deamination of all substrates was uniformly sensitive to inhibition by clorgyline and relatively insensitive to deprenyl. These data together with the observations of simple sigmoid curves for the inhibition of tyramine deamination by both inhibitors suggest that C6 glial cells contain mainly monoamine oxidase type A, which previously had been suggested to be primarily an intraneuronal MAO type. As these findings are in agreement with other studies of brain MA0 activity in mitochondria separated from neuronal vs glial cell preparations, they help explain why MA0 activity measured with some substrates may be little affected by lesions or by drugs producing nerve ending degeneration.
54 citations
TL;DR: MAO in human placenta differs from that in other organs, such as liver, brain and plasma from the standpoint of the substrate specificity and the inhibitor sensitivity.
TL;DR: The possibility that malfunction of the enzyme monoamine oxidase (E.C.4.4., MAO) could lead to aberrations in the catabolism of biogenic amines in the central nervous system and give rise to certain mental abnormalities is explored.
Abstract: This article explores the possibility that malfunction of the enzyme monoamine oxidase (E.C. 1.4.3.4., MAO) could lead to aberrations in the catabolism of biogenic amines in the central nervous system and give rise to certain mental abnormalities. No conclusive evidence could be presented to substantiate this. Data on the normal function of the enyzme (for example its existence in multiple forms, the control of MAO activity by hormones or the independent development of MAO activities towards different substrates during maturation) are reviewed.
TL;DR: Phenylethylamine is inactivated in a single passage through rat lung tissue by a process of uptake and deamination by a monoamine oxidase ‘type B’ which appears to operate independently in the organized tissue.
Abstract: Phenylethylamine is inactivated in a single passage through rat lung tissue by a process of uptake and deamination by a monoamine oxidase 'type B'. This enzyme is particularly susceptible to inhibition by deprenil and less sensitive to clorgyline. The monoamine oxidase of the lung, like that of other rat tissues, can be differentiated into 'type A' and 'type B' which appear to operate independently in the organized tissue.
TL;DR: Lineweaver-Burk plots revealed that chlordime form, demethylchlordimeform, and 4′-chloro- o -formotoluidide were competitive inhibitors of the oxidative deamination of β-phenylethylamine, tyramine, dopamine, tryptamine, and serotonin.
TL;DR: It is suggested that iron is necessary either for the synthesis of monoamines oxidase apoenzyme or is a cofactor for an enzyme which attaches flavin-adenine dinucleotide covalently to the monoamine oxidase Apoenzyme.
Abstract: 1. Monoamine oxidase activity in platelets prepared from the blood of patients with iron-deficiency anaemia was significantly lowered when compared with that in platelets from normal subjects. 2. The Km values of the platelet enzyme for the substrates dopamine, 5-hydroxytryptamine, phenylethylamine and kynuramine were similar for the platelet enzyme from iron-deficient and normal groups. 3. Heat-in-activation studies showed that the platelet monoamine oxidase from iron-deficient subjects was more labile to this treatment, when compared with the platelet enzyme from normal subjects. 4. The sensitivity of platelet monoamine oxidase to the inhibitors, clorgyline and deprenil, was increased in iron-deficiency anaemia. 5. Binding studies with the 14C-binding irreversible monoamine oxidase inhibitor, deprenil, showed that the amount of enzyme capable of binding this inhibitor was lowered by 48% in platelets from iron-deficient patients when compared with platelets from normal subjects. 6. The results show that there is a lowered amount of active enzyme in platelets from iron-deficient subjects. It is suggested that iron is necessary either for the synthesis of monoamine oxidase apoenzyme or is a cofactor for an enzyme which attaches flavin-adenine dinucleotide covalently to the monoamine oxidase apoenzyme.
TL;DR: Kinetic studies of cardiac and liver MAO after thyroxine-treatment showed an unaltered Km for benzylamine but a change in KM for serotonin, which may indicate a discriminative action of thyroid hormones on different forms of MAO.
Abstract: Male and female rats of 2 age groups were given subcutaneous injections of L-thyroxine (500 μg/kg) at 12 h intervals for a period of 10 days. The activity of monoamine oxidase (MAO) in normal and thyrotoxic rats was studied with two substrates: benzylamine and serotonin. The results showed that a thyroxine effect on cardiac and liver MAO activity is dependent on the substrate used in the assay. Kinetic studies of cardiac and liver MAO after thyroxinetreatment showed an unaltered Km for benzylamine but a change in Km for serotonin. Both findings may indicate a discriminative action of thyroid hormones on different forms of MAO. The possible presence of a soluble activator and inhibitor for MAO was investigated. (Endocrinology 98: 761, 1976)
TL;DR: A general model for the inhibitor pharmacophore is proposed: potent MAO of an aromatic ring; electron-withdrawing groups on the aromatic ring or replacing the phenyl ring with certain types of heterocyclic rings will tend to increase the potency.
Abstract: Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hammet sigma constants and electronic indices from molecular orbital calculations. Based on these correlations and previously published data on other classes of MAO inhibitors, a general model for the inhibitor pharmacophore is proposed: potent MAO of an aromatic ring; electron-withdrawing groups on the aromatic ring or replacing the phenyl ring with certain types of heterocyclic rings will tend to increase the potency.
TL;DR: Tryptoline, a metabolite of tryptamine, competitively inhibits serotonin accumulation in nuclei-free homogenate of rat “forebrains” after intraventricular injection and elicits an increase of serotonin levels in the same part of the brain whereas the monoamine oxidase activity is not altered.
Abstract: Tryptoline, a metabolite of tryptamine, competitively inhibits serotonin accumulation in nuclei-free homogenate of rat "forebrains". After intraventricular injection the drug elicits an increase of serotonin levels in the same part of the brain whereas the monoamine oxidase activity is not altered.
Journal Article•
TL;DR: The monoamine oxidase in the liver was found to have a significantly higher molecular turnover for tyramine and beta-phenylethylamine than that in the brain, heart and kidney.
Abstract: Molecular turnover numbers of the different forms of monoamine oxidase in rat liver were estimated for serotonin, tyramine and beta-phenylethylamine by titration with irreversible inhibitors. The 'A' form was found to have a much higher turnover number for serotonin and a lower turnover number for beta-phenylethylamine than the 'B' form, while the turnover numbers for tyramine were in the same order of magnitude for both forms. The monoamine oxidase in the liver was found to have a significantly higher molecular turnover for tyramine and beta-phenylethylamine than that in the brain, heart and kidney. It was calculated that the 'A' form of monoamine oxidase amounted to about 20% and the 'B' form to about 80% of the total amount of monoamine oxidase in the rat liver mitochondrial preparation. The number of molecules per mitochondrion was also calculated.
TL;DR: A simple fluorometric assay for monoamine oxidase (MAO) activity towards beta-phenylethylamine (PEA) was devised, and the disappearance of PEA fluorometrically was measured, completely inhibited by pargyline, a potent inhibitor of MAO.
Abstract: A simple fluorometric assay for monoamine oxidase (MAO) [EC 1.4.3.4] activity towards beta-phenylethylamine (PEA) was devised. The procedure consists in measuring the disappearance of PEA fluorometrically. The disappearance of PEA was completely inhibited by pargyline, a potent inhibitor of MAO. MAO activity for PEA was linear with 10 mg to 100 mg of liver tissue in 3 ml of reaction mixture for up to 90 min of incubation. Using this method, the V max values and the apparent Km values of MAO for PEA in several rat tissues were determined, and compared with those for benzylamine and 5-hydroxytryptamine (5-HT).
TL;DR: The selectivity found when these inhibitors react with monoamine oxidase in vitro is also apparent when the enzyme from rats which have received single doses of the compounds is studied, but is less clearcut after repeated administration.
TL;DR: Hyperactivity after monoamine oxidase inhibitor/ l -tryptophan may represent a pre-ictal phenomenon and may not constitute an appropriate model for the reputed antidepressant action of monoamine oxidation enzyme combinations in depressive illness.
TL;DR: The metabolic interaction of three secondary amines and three nitrogen-containing metabolites of safrole (tertiary amino propiophenones) with rat liver mitochondrial monoamine oxidase systems was studied in vitro employing [7-14C] benzylamine--HCl as a substrate.
TL;DR: The influence of amitriptyline, a prototype of tricyclic antidepressants, on the selected variables (Km, V, I50), was studied and concentrations which showed a pronounced effect on the enzyme characteristics are significantly higher than plasma levels of the drug found under therapeutic conditions.
Abstract: Some biochemical characteristics such as substrate specificity, substrate affinity and inhibitor sensitivity of monoamine oxidase of human blood platelets were investigated. Tyramine, tryptamine and beta-phenylethylamine were used as substrates. The apparent Michaelis constants, maximal velocity rates and I50 for the inhibitor tranylcypromine were determined. The data were analyzed according to Lineweaver-Burk and Dixon. The influence of amitriptyline, a prototype of tricyclic antidepressants, on the selected variables (Km, V, I50), was studied. The parameters investigated showed remarkably low interindividual differences when healthy volunteers were tested. The inhibitor activity of amitriptyline towards platelet monoamine oxidase depends on the substrate used. Amitriptyline concentrations which showed a pronounced effect on the enzyme characteristics are significantly higher than plasma levels of the drug found under therapeutic conditions.
TL;DR: It is suggested that the fundamental mechanism underlying the pharmacological and biochemical effects of PF-257 may be its activity to decelerate catecholamine metabolism in the brain without inhibiting the enzymes participating in the metabolic degradation of the amines.
Abstract: The effects of 1, 2-benzisoxazole-3-acetamidoxime hydrochloride (PF-257), a novel psychotropic agent possessing the pharmacological properties similar, in some respects, to those of tricyclic antidepressants or monoamine oxidase inhibitors, on the metabolism of brain monoamines were studied in rats. A single large dose or repeated doses of PF-257 caused a slight but significant increase in brain norepinephrine level without affecting the contents of dopamine and serotonin. Like monoamine oxidase inhibitors, PF-257 prevented and reversed the decrease in brain norepinephrine induced by reserpine but it lacked the property to inhibit monoamine oxidase in the brain. Unlike tricyclic antidepressants, the compound was devoid of the capacity to inhibit norepinephrine uptake in vitro. Administration of PF-257 in combination with L-β-3, 4-dihydroxyphenylalanine (L-DOPA) enhanced the increase in brain dopamine without influencing the amount of the amino acid incorporated into the brain. At relatively small doses, PF-257 reduced the rate of decline of brain norepinephrine and dopamine levels following α-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, and also decreased the levels of brain 3-methoxy-4-hydroxy-phenylethyleneglycol sulfate and homovanillic acid, major metabolites of brain norepinephrine and dopamine, respectively. Thus, it is suggested that the fundamental mechanism underlying the pharmacological and biochemical effects of PF-257 may be its activity to decelerate catecholamine metabolism in the brain without inhibiting the enzymes participating in the metabolic degradation of the amines.
TL;DR: 4-methoxyphenethylamine and its N-methylated homologs inhibit the monoamine oxidase-catalyzed deamination of both tyramine and tryptamine.