New inhibitor of monoamine oxidase.
TL;DR: This work includes in vitro action of this inhibitor on rat liver mitochondria as well as in vivo inhibition of monoamine oxidase of mouse brain and the liver.
Abstract: THE following is the initial report of a structurally unique monoamine oxidase inhibitor, N-benzyl-N-methyl-2-propynylamine hydrochloride (A19120). This work includes in vitro action of this inhibitor on rat liver mitochondria as well as in vivo inhibition of monoamine oxidase of mouse brain and the liver.
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TL;DR: No marked changes were observed in the activity of polyamine oxidase in rat liver after partial hepatectomy, carbon tetrachloride poisoning, and after treatment with growth hormone or thioacetamide, conditions which are known to alter profoundly the metabolism and accumulation of polyamines.
Abstract: A novel enzyme responsible for the oxidation of spermidine and spermine has been found in rat liver. Spermidine is shown to be degraded to putrescine and 3-aminopropionaldehyde, and spermine to be cleaved to spermidine and 3-aminopropionaldehyde. A single enzyme catalyzing both reactions and designated as polyamine oxidase has been purified 4000-fold to electrophoretic homogeneity. Polyamine oxidase appears to be a flavoprotein, containing flavin adenine dinucleotide (FAD) as a prosthetic group. Hydrogen peroxide is evolved in the reaction and no other electron acceptors except molecular oxygen have been found. The molecular weight of the enzyme was approximately 60 000 and the sedimentation coefficient 4.5 S. The enzyme appears to be a single polypeptide chain since no evidence for structural subunits was obtained. Polyamine oxidase was sensitive to sulfhydryl and carbonyl group reagents. The optimum pH value for the oxidation of polyamines was close to 10. The reaction velocities were enhanced by various aldehydes, especially certain aromatic aldehydes. Polyamine oxidase appears to be localized in peroxisomes of liver cells, although the existence of an isoenzyme in the cytosolic fraction was not definitively ruled out. No marked changes were observed in the activity of polyamine oxidase in rat liver after partial hepatectomy, carbon tetrachloride poisoning, and after treatment with growth hormone or thioacetamide, conditions which are known to alter profoundly the metabolism and accumulation of polyamines.
311 citations
TL;DR: Four molecular forms of monoamine oxidase exist in at least four molecular forms in different areas of the human brain and may have important clinical implications, perhaps reflecting their relative ability to degrade different monoamine substrates in vivo.
Abstract: Monoamine oxidase exists in at least four molecular forms in different areas of the human brain. Variations in their enzymatic properties may have important clinical implications, perhaps reflecting their relative ability to degrade different monoamine substrates in vivo.
221 citations
TL;DR: An approach is offered which is in better accord with the characteristics of MAO and which some compounds belonging to this group are considerably more effective therapeutically than others.
Abstract: THE enzyme monoamine oxidase (monoamine : O2 oxido-reductase (deaminating), EC 1.4.3.4) (MAO) is likely to be concerned in the metabolism of known or suspected central nervous system transmitters such as nor adrenaline, dopamine and 5-hydroxytryptamine. In the therapy of depressive disease, drugs are used which are able to inhibit MAO and it is thought that they owe their beneficial effect to this ability and to the resulting accumulation of amines. It is found, however, that some compounds belonging to this group are considerably more effective therapeutically than others1,2 and no fully satisfactory explanation has been offered. We now offer an approach which we think in better accord with the characteristics of MAO.
162 citations
TL;DR: Key pathways discussed include neurotransmission, neuroinflammation, clock gene machinery pathways, oxidative stress, role of neurotrophins, stress response pathways, the endocannabinoid and endovanilloid systems, and the endogenous opioid system.
Abstract: Major depressive disorder (MDD) is considered a serious public health issue that adversely impacts an individual’s quality of life and contributes significantly to the global burden of disease. The clinical heterogeneity that exists among patients limits the ability of MDD to be accurately diagnosed and currently, a symptom-based approach is utilized in many cases. Due to the complex nature of this disorder, and lack of precise knowledge regarding the pathophysiology, effective management is challenging. The aetiology and pathophysiology of MDD remain largely unknown given the complex genetic and environmental interactions that are involved. Nonetheless, the aetiology and pathophysiology of MDD have been the subject of extensive research, and there is a vast body of literature that exists. Here we overview the key hypotheses that have been proposed for the neurobiology of MDD and highlight the need for a unified model, as many of these pathways are integrated. Key pathways discussed include neurotransmission, neuroinflammation, clock gene machinery pathways, oxidative stress, role of neurotrophins, stress response pathways, the endocannabinoid and endovanilloid systems, and the endogenous opioid system. We also describe the current management of MDD, and emerging novel therapies, with particular focus on patients with treatment-resistant depression (TRD).
94 citations
TL;DR: Conjugated (sulphonyloxy) dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were synthesized from free DOPAC and HVA and used as reference compounds in their fluorimetric determination in rat brain (detection limit 0.2 nmol/g).
Abstract: — Conjugated (sulphonyloxy) dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were synthesized from free DOPAC and HVA and used as reference compounds in their fluorimetric determination in rat brain (detection limit 0.2 nmol/g). The conjugated DOPAC and HVA form 29 and 36% of the total DOPAC and HVA found in rat striatum, respectively. Dopamine (DA) metabolism was studied in the rat striatum by following the decline of both free and conjugated DOPAC and HVA after treatment with pargyline (100mg/kg. i.p.) either alone or in combination with tropolone (100 mg/kg, i.p.). or from the accumulation of the free and conjugated acids after treatment with probenecid (100-500mg/kg. i.p.). The rates of decline were analysed by a non-linear curve fitting method using a simple model of DA metabolism that postulates the formation of the conjugates exclusively from the free acids, and HVA from DOPAC, with first order kinetics and single open compartments only. The curves computed all passed through the s.e.m. of every experimental point. The rate constants thus found indicate that DOPAC turnover is about 23nmol/g/h. Of this about 16 nmol/g/h are O-methylated to HVA, about 6 nmol/g/h are conjugated and less than 1 nmol/g/h is eliminated as free DOPAC. Of the HVA formed, about 8.5nmol/g/h are conjugated and about 7.5 nmol/g/h eliminated as free HVA. The conjugates accumulated after treatment with probenecid (1 h) faster than the free acids. The maximal accumulation of all four metabolites found (21 nmol/g/h) approximates the total turnover of DOPAC.
91 citations
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Book•
01 Jan 1962
TL;DR: In this article, Microdiffusion analysis and volumetric error was used to detect micro-diffusion errors in the context of micro-scale analysis of the volumetry data.
Abstract: Microdiffusion analysis and volumetric error , Microdiffusion analysis and volumetric error , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
2,357 citations
383 citations
TL;DR: Harmaline and related compounds have been shown to be potent inhibitors of monoamine oxidase effecting 50 per cent inhibition of serotonin metabolism at 10−6 M.
177 citations