Showing papers on "Monoamine oxidase B published in 1977"
TL;DR: It is demonstrated that, as far as DA oxidation is concerned, man may be different from rat: in two sites the authors have investigated, platelet and brain, DA is preferentially deaminated by an enzyme with the characteristics of MAOB.
Abstract: DURING the past decade, the central neurotransmitter, dopamine (DA), has been much studied for it is known to be involved in certain human disease states, Parkinsonism1 preeminently, and rather more inferentially, schizophrenia2. DA is metabolised by monoamine oxidase (MAO)3, which catalyses the oxidative deamination of a wide range of monoamines4,5, including the neurotransmitters noradrenaline (NA) and 5-hydroxytryptamine (5-HT), and other amines such as tyramine, tryptamine and phenylethylamine (PEA). On the basis of animal studies with the inhibitors, clorgyline6, and later deprenil7, MAO has been classified into two types, A and B. By definition, type A is selectively inhibited by clorgyline and type B by deprenil. In general, type A acts on 5-HT6 while type B prefers PEA8. In the rat, DA is preferentially deaminated by MAOA9–11. It thus seemed paradoxical that, in the treatment of Parkinsonism, addition of the MAOB inhibitor, deprenil, to a DA-generating drug combination should produce further therapeutic benefit12. In this report, we reconcile these apparently conflicting observations by demonstrating that, as far as DA oxidation is concerned, man may be different from rat: in two sites we have investigated, platelet and brain, DA is preferentially deaminated by an enzyme with the characteristics of MAOB.
325 citations
TL;DR: A new method has been developed for the separation of histamine and its metabolites after intracisternal injection of [3H]histamine into the rat brain, involving solvent extraction and subsequent thin‐layer chromatography.
Abstract: — A new method has been developed for the separation of histamine and its metabolites after intracisternal injection of [3H]histamine into the rat brain, involving solvent extraction and subsequent thin-layer chromatography.
The effect of graded doses of the MAO inhibitors deprenil and pargyline, which at relatively low doses inhibit preferentially the B form (phenethylamine deaminating) of the enzyme, and clorgyline, which mainly inhibits the A form (serotonin, noradrenaline and dopamine deaminating) on the brain levels of intracisternally injected [3H]histamine and its labelled metabolites was studied and compared to MAO A and B activity as determined with the substrates serotonin and phenethylamine, respectively. In addition, the time-course of the effects of a single dose of pargyline (50mg/kg subcutaneously) was investigated. No [3H]imidazoleacetic acid could be detected in any of the control or treated animals. [3H]Histamine accounted for 9–12% of the total extracted radioactivity and this was not altered significantly by pretreatment with any of the MAO inhibitors up to high doses, at which both MAO A and B activities were completely inhibited.
In the controls, 40–43% of the total extracted radioactivity was [3H]methylhistamine and 28–30% was [3H]methylimidazoleacetic acid. Deprenil and pargyline caused [3H]methylhistamine levels to increase in a dose-dependent manner up to about 150% of control levels and those of [3H]methylimida-zoleacetic acid to decrease concomitantly to about 10% of control levels. Clorgyline in doses up to 10 mg/kg subcutaneously (s.c.) had no effect on the levels of these two metabolites. The dose-response curves of the effects of deprenil and pargyline on [3H]methylimidazoleacetic acid levels were congruent with those of the MAOI effects on MAO B activity and not with those on MAO A activity.
Pargyline (50 mg/kg s.c.) had a long lasting effect on the accumulation of [3H]methylhistamine and [3H]methylimidazoleacetic acid. Recovery occurred within 21 days, and the half-lives observed were 5.3 and 5.6 days, respectively. This compares well to the half-life for the recovery of MAO B activity reported earlier after the same dose of pargyline (5.5 days).
These results suggest that methylhistamine is metabolized selectively by MAO B in rat brain. Moreover, the fact that clorgyline, at doses where phenethylamine deamination is already considerably inhibited, did not affect the deamination of methylhistamine, suggests that the latter is an even more selective substrate for MAO B than phenethylamine itself.
Therefore, small doses of deprenil (0.3–3 mg/kg s.c.) or pargyline (1–3 mg/kg) can be used to influence histamine catabolism without interfering with catecholamine or serotonin deamination.
73 citations
71 citations
64 citations
TL;DR: A series of serotonin and phenethylamine analogs were tested for their ability to differentially inhibit type A or B monoamine oxidase in rat hypothalamus and the most specific and potent effects were shown by several tetrahydro‐β‐carbolines which competitively inhibited the oxidative deamination of serotonin at micromolar concentrations.
Abstract: — A series of serotonin and phenethylamine analogs were tested for their ability to differentially inhibit type A or B monoamine oxidase (EC 1.4.3.4) in rat hypothalamus. The most specific and potent effects were shown by several tetrahydro-β-carbolines which competitively inhibited the oxidative deamination of serotonin at micromolar concentrations. In contrast, effective inhibition of phenethylamine deamination was observed only at or near millimolar concentrations of these drugs. Significant reductions of type A but not type B MA0 activity were also observed after administration of 25–100 mg/kg, i.p., of tetrahydro-β-carboline and its 6-methoxy derivative.
60 citations
50 citations
TL;DR: Elevated blood serotonin, perhaps secondary to reduced platelet MAO, has been reported in a group of chronic schizophrenic patients, but any relationship between platelet serotonin and MAO either in agroup of unmedicated chronic schizophrenia patients or in a groups of schizoaffective patients is failed to find.
Abstract: Elevated blood serotonin, perhaps secondary to reduced platelet MAO, has been reported in a group of chronic schizophrenic patients. We have failed to find elevated platelet serotonin, or any relationship between platelet serotonin and MAO either in a group of unmedicated chronic schizophrenic patients or in a group of schizoaffective patients. Possible reasons for these discrepancies are discussed.
38 citations
36 citations
TL;DR: The data support the view that impulse flow in DA neurons facilitates the effect of (+)-amphetamine on DA release and DA synthesis, and inhibition of catecholamine synthesis after high doses of (+-amphetamine may be due to an increase in cytoplasmatic DA concentration causing end-product inhibition of tyrosine hydroxylase.
Abstract: The interaction of (+)-amphetamine with haloperidol andγ-butyrolactone on synthesis of monoamines in rat brain regions was investigated using anin vivo method, in which the accumulation of dopa and 5-hydroxytryptophan (5-HTP) was measured after inhibition of the aromatic amino acid decarboxylase by means of 3-hydroxybenzylhydrazine. The accumulation of 3-methoxytyramine (3-MT) after inhibition of the monoamine oxidase with pargyline was taken as an indicator of thein vivo release of dopamine (DA) into the extraneuronal space.
32 citations
22 citations
TL;DR: A tenable hypothesis is that the manipulation in the composition of the monoamine oxidase binding forms through intimate lipid-protein interactions, which has been amply demonstrated in many biomembrane systems to be functionally important might be the underlying regulatory mechanism in vivo.
TL;DR: It is suggested that desynchronization of EEG induced by deprenyl is more likely due to increased endogenousβ-phenylethylamine than to increased concentration of endogenous DA in the brain.
Abstract: Electrophysiological and biochemical effects of deprenyl andβ-phenylethylamine were studied in rats, d, l-Deprenyl, l-deprenyl (4–16 mg/kg) andβ-phenylethylamine (75 mg/kg) induced a desynchronization of ECoG after i.p. administration of drugs. The effects lasted several hours. The biochemical analysis indicate that d, l-deprenyl (4 mg/kg) nearly doubled the concentration of brain dopamine (DA) while the concentration of noradrenaline was not altered. The maximal increase was reached at 60 min and the enhanced concentration of DA stayed at this level up till 180 min after administration of drug. Treatment of rats withα-methyl-p-tyrosine (200 mg/kg) did not antagonize a deprenyl induced desynchronization of ECoG. However, even low dose of haloperidol (0.1 mg/kg) abolished the arousal effect of d, l-deprenyl andβ-phenylethylamine. It is suggested that desynchronization of EEG induced by deprenyl is more likely due to increased endogenousβ-phenylethylamine than to increased concentration of endogenous DA in the brain.
TL;DR: The results indicate that the effects of pre-incubation time and the enzyme: drug ratio on inhibition of MAO by clorgyline should be fully recognized when using the drug to indicate multiple forms in animal tissues.
TL;DR: Several substituted styrylquinazolones were synthesized and tested for their ability to inhibit the oxidative deamination of kynuramine by monoamine oxidase from the rat brain and Quinzhydrazide group were found to be better inhibitors than their corresponding precursor esters.
TL;DR: Optimal conditions for deamination of 5-hydroxytryptamine in rat skeletal muscle were determined and the approximate proportion of muscle homogenate MAO which is present in sympathetic nerves was found to be 18 per cent, as determined by treating rats with 6-hydroxydopamine and quantifying the decrease in activity.
TL;DR: Findings indicate that the full antidepressive effect, which only appears after the first 3 weeks of long term treatment, cannot be caused by the inhibition of MAO.
Abstract: Amitriptyline, at a concentration of 10(-5) M, inhibits the oxidative deamination of phenylethylamine, tyramine and tryptamine (by 40, 16, and 8 percent, respectively) by rat brain MAO. After the long term administration of amitryptyline, even at a dosage of 20 mg per kg body weight twice daily, there was no detectable influence on the biochemical properties of MAO. These findings indicate that the full antidepressive effect, which only appears after the first 3 weeks of long term treatment, cannot be caused by the inhibition of MAO.
TL;DR: The cactus alkaloid 3,4-dimethoxyphenethylamine and its naturally occurring N-methylated homologs inhibited the deamination of tyramine and tryptamine by rat brain monoamine oxidase, but the beta-hydroxylated derivatives of this series failed to inhibit the action of monoamines oxidase.
TL;DR: The specific activity of monoamine oxidase in muscle homogenates was higher for benzylamine than for serotonin, and the total concentration of monoamines in human skeletal muscle was found to be 90% type B and 10% type A.
TL;DR: There was an apparent positive correlation between the sympathetic character of peripheral nerves and the presence of type A monoamine oxidase activity in the superior cervical ganglion and vagus nerve of the albino rabbit.
Journal Article•
TL;DR: Results provide evidence for the possible existence of heterogenous subpopulations of lung mitochondria differing in sedimentation behavior and containing monoamine oxidase with different substrate specificity and inhibitor sensitivity.
TL;DR: Atropine sulphate was found to inhibit rat brain and heart monoamine oxidase in vitro and the enzyme-inhibitor dissociation constant (K i) found to be 7.36 × 10 −3 M and 5.5 × 10−3 M, respectively.
TL;DR: The selective inhibitor of type A monoamine oxidase (MAO) chlorglyline prevented the appearance of ability to deaminate histamine or AMP, qualitatively new properties for this object, in fragments of mitochondrial membranes from rat liver when incubated under aerobic conditions.
Abstract: The selective inhibitor of type A monoamine oxidase (MAO) chlorglyline (unlike deprenil, an inhibitor of type B MAO) prevented the appearance of ability to deaminate histamine or AMP, qualitatively new properties for this object, in fragments of mitochondrial membranes from rat liver when incubated under aerobic conditions. The qualitative transformation of the catalytic properties under the influence of oxidizing agents is evidently undergone by type A but not by type B MAO.
01 Jan 1977