Showing papers on "Monoamine oxidase B published in 1978"

Deprenyl administration in man: A selective monoamine oxidase B inhibitor without the ‘cheese effect’

Abstract: After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.

Psychological correlates of monoamine oxidase activity in normals.

Abstract: This study replicates and extends earlier work by finding that low levels of platelet monoamine oxidase (MAO) activity correlate with sensation seeking, high ego strength, positive affect, and high leisure time activity levels, somewhat similar psychological correlates also being found for plasma am

Amphetamine and 2-phenylethylamine in post-mortem Parkinsonian brain after (-)deprenyl administration.

Abstract: Deprenyl is an inhibitor of monoamine oxidase type B, the enzyme responsible for 2-phenylethylamine oxidation, and is used in conjunction with L-Dopa therapy in Parkinson's disease. Post-mortem studies in human brain tissue have shown that after (-)deprenyl administration to parkinsonian patients amphetamine is present in concentrations up to 56 ng/g. It also could be shown that phenylethylamine concentrations are substantially increased in such patients.

Absence of "cheese effect" during deprenyl therapy: some recent studies.

Abstract: Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the "cheese effect" in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with "orthodox" MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.

Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine.

Abstract: A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.

Platelet monoamine oxidase activity in Huntington's chorea.

Abstract: The possibility that genetically determined abnormalities in the monoamine oxidase of certain central nervous system aminergic neurones may play a part in the pathology of Huntington's chorea was investigated using human platelet monoamine oxidase. Significantly elevated monoamine oxidase activity was found in male patients compared to control subjects suggesting this may be a screening test for this disorder. Low monoamine oxidase activity was associated with a better clinical response to drugs.

2-(Alkoxyaryl)-2-imidazoline monoamine oxidase inhibitors with antidepressant activity.

Abstract: Unlike the related noncyclic amidines which are broad-spectrum cestocides, a number of 2-imidazolines substituted in the 2 position by alkoxyaryl groups were not highly active in screening tests against the mouse tapeworms Hymenolepsis nana and Oochoristica symmetrica. Certain of the 2-(4-alkoxynaphthyl)-2-imidazolines and 2-(6-alkoxy-2-naphthyl)-2-imidzolines, however, had activity interpreted as antidepressant in the mouse. This activity paralleled in vitro irreversible inhibitory activity against mouse brain MAO for those where no substitution is present on the imidazoline ring. This irreversibility probably has a different origin from that postulated to explain the irreversible MAO inhibition of proparglic, cyclopropyl, and other "chemically reactive" MAO inhibitors.

Monoamine oxidase activities for serotonin and tyramine in individual limbic and lower brain stem nuclei of the rat

Abstract: MONOAMINE oxidase (MAO; EC 1.4.3.4.) is a major enzyme in the catabolism of the putative neurotransmitter monoamines. During the past decade, it has been suggested that M A 0 in the brain exists in multiple forms (YOUDIM, 1972) and has been classified into two forms, type A and type B, by studies with substrate-specific inhibitors (JOHNSTON, 1968; YANG & NEFF, 1974). Some workers have reported the discriminative action of several hormones on dimerent forms of M A 0 (TONG & D~ORIO, 1976; YOUDIM & HOLZBAUER, 1976). the differential maturation of the two types of M A 0 (JOURDIKIAN et al., 1975) and different effects of selective M A 0 inhibitors on some behaviours (FUENTES & NEW, 1975) and drugs (Rom & GILLIS, 1975). However, little information referring to the physiological significance of this multiplicity in the discrete brain regions was reported. The limbic system consists of many nuclei and areas where catecholaminergic and serotonergic pathways are projected from the cell bodies located in the lower brain stem (DAHLSTR~M & FUXE, 1964; UNGERSTEDT. 1971). The biogenic amines in the brain are known to play different roles in various autonomic, neuroendocrine and behavioural functions. The present study describes the distribution of M A 0 activities towards serotonin which is a specific substrate for MAOA and tyramine which is a substrate for both MAO-A and MAO-B in individual limbic regions, main monoamine-containing cell groups and some hypothalamic areas, using the micromethod with freeze-dried sections (UCHImRA et a/., 1974; HIRANO et a/., 1975).

The influence of L-tryptophan and monoamine oxidase inhibitors on catecholamine metabolism in rat brain.

Abstract: 1. L-Tryptophan (100 mg/kg) was administered to rats with or without pretreatment with a monoamine oxidase inhibitor and the concentration of 5-hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3-methoxy 4-hydroxyphenyl glycol, normetanephrine, noradrenaline and dopamine measured in whole brain one hour later. 2. L-Tryptophan increased the concentration of 5-hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3-methoxy 4-hydroxyphenyl glycol and normetanephrine. The concentration of noradrenaline did not change whilst that of dopamine increased significantly. 3. In animals pretreated chronically with a monoamine oxidase inhibitor, tryptophan increased the concentration of dihydroxyphenylacetic acid and homovanillic acid compared to monoamine oxidase alone. 4. The results suggest either a release of dopamine and noradrenaline by 5-hydroxytryptamine, with a compensatory increase in their synthesis, or an increase in the firing of dopaminergic and noradrenergic neurones after L-tryptophan.

Selectivity among monoamine oxidase inhibitors and its possible importance for development of antidepressant drugs

Abstract: 1. 1. Inhibitors of monoamine oxidase (MAO) may show a high degree of selectivity toward various MAO forms or toward the enzyme in specific tissues or cells. The combination of selective inhibitors with other drugs or with amines or amine precursors may further enhance their selectivity. 2. 2. Most MAO inhibitors in clinical use were introduced before this selectivity and its bases were well understood, and little systematic effort appears to have been directed toward development of MAO inhibitors with optimum therapeutic benefit and minimum side effects based on selective actions. The potentials of MAO inhibitors in the treatment of mental depression and other disorders may need to be re-assessed in light of current knowledge.

Inhibition of human brain type B monoamine oxidase by tricyclic psychoactive drugs.

Abstract: The ability of a variety of tricyclic psychoactive drugs to inhibit human brain mitochondrial type B monoamine oxidase as measured by phenylethylamine (PEA) deamination was examined in vitro . At 50 µM all drugs tested, with the exception of chlorpromazine sulfoxide and imipramine N -oxide, inhibited this reaction between 40.8% and 78.4%. Lineweaver-Burk plots for imipramine, chlorpromazine, and chlorprothixene inhibition of PEA deamination displayed a mixed inhibition pattern when incubations were performed at normal atmospheric oxygen tension. When the oxygen concentration was elevated, inhibition of this reaction by each of the three drugs became more competitive. These results suggest that these drugs inhibit the B form of monoamine oxidase by binding to both the oxidized and reduced forms of the enzyme. Inhibition of monoamine oxidase by imipramine and desmethylimipramine increased as the pH was raised from 7.0 to 9.0, but because the ratio of the increase remained constant for the two drugs, inhibition probably was independent of the degree of ionization of the side chain aliphatic amine. It was also found that the optimal pH for human brain mitochondrial deamination of PEA shifted from 8.0 to 8.5 as the oxygen concentration was increased. ACKNOWLEDGMENT The author wishes to thank Ms. Barbara Eddy for her excellent technical assistance during the course of this investigation.

The influence of respiratory state on monoamine oxidase activity in rat liver mitochondria.

Abstract: Changes in the respiratory state of rat liver mitochondria caused significant changes (up to 10-fold) in the rates of oxidative deamination of tyramine, indicating interactions between the inner coupling membrane and the monoamine oxidase sites in the outer membrane, and suggesting the possibility that monoamine oxidase is regulated by the thermodynamic state of the mitochondria.

Interaction of 5,6- and 5,7-dihydroxytryptamine with tissue monoamine oxidase.

Abstract: Since the discovery by Thoenen and Tranzer 1s that 2,4,5-trihydroxyphenylethylamine (“6-hydroxydopamine;” 6-OH-DA) caused a long-lasting depletion of noradrenaline (NA) in peripheral organs by destruction (“chemical sympathectomy”) of noradrenergic axons, there has been continuing interest in the mechanism that is responsible for its unique selective neurotoxicity. Based on experimental evidence, two main theories for the molecular mechanism of 6-OH-DA toxicity have been proposed: the theory that oxidation products of 6-OH-DA undergo irreversible, covalent binding to functionally indispensable nucleophiles in proteins and the postulate that the autoxidation of 6-OH-DA gives rise to oxygen and hydroxyl radicals and to hydrogen peroxide, which are the actual species responsible for neuronal damage.’ The former theory has received considerable support by three recent one of which has impressively demonstrated that covalent attack of quinoid 6-OH-DA intermediates to the active site of a defined enzyme in catecholamine metabolism, catechol-0-methyltransferase, is correlated with and probably responsible for its capability to irreversibly inactivate the enzyme.8 The suggestion by Borchardt 6 that an aminochrome-like intermediate of 6-OH-DA (5,6-o-indolquinone) was one of the more important candidates for such a role in inactivating functional groups in this enzyme focused our attention on the possibility that the neurotoxic potential of 5,6-dihydroxytryptamine (5,6-DHT), a drug with known preferential action on central 5-hydroxytryptamine (5-HT) neur o n ~ , ~ ~ lo might be due to an analogous mechanism. Therefore, its interaction with the most important enzyme in serotonin catabolism, monoamine oxidase (MAO), was studied in vitro and in vivo and correlated with its capability to undergo protein binding. From the beginning of these studies, it was anticipated that 5,7-dihydroxytryptamine (5,7-DHT), which has a selective damaging action on central 5-HT fibers similar to that of 5,6-DHT but less unselective cytotoxic side effects,” should have qualitatively different effects on this enzyme due to its differing physicochemical properties, despite its similarity in causing neuronal damage. The results of the present study substantiate these suspected differences in the behavior of 5,6-DHT and 5,7-DHT but suggest at the same time that the final process that results in neurotoxicity is similar for both drugs, namely, covalent binding of reactive intermediates to nucleophiles in proteins, disregarded important differences in the initial oxidation and metabolism of 5,6-DHT and 5.7-DHT in vivo.

Biochemical and behavioural studies of monoamine oxidase inhibition.

Abstract: The effects of dl-N-propargkl ampheta-mine on monoamine oxidase in rat brain have been studied. It was found that i.p. injection of this compound produced a marked stereotyped response. It was also found to potentiate the stereotypy produced by amphetamine. Subsequent examination of monamine oxidase activity in the brains of the animals showed substantial inhibition of the B form of this enzyme (as judged by 2-phenylethylamine oxidation) but no effect on the A form. The optical isomers of N-propargyl amphetamine have been prepared and their inhibitory activityin vitro against monamine oxidase in rat liver mitochondria has been assessed. The l-isomer was found to be a better inhibitor than the d-isomer.