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Keith F. Tipton - One of the best experts on this subject based on the ideXlab platform.
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Species Differences in the Selective Inhibition of Monoamine Oxidase (1-methyl-2-phenylethyl)hydrazine and its Potentiation by Cyanide
Neurochemical Research, 2007Co-Authors: Zakia Ben Ramadan, Maria L. Wrang, Keith F. TiptonAbstract:The potentiating effects of cyanide on the inhibition of rat liver mitochondrial monoamine oxidase-A & B and of ox liver mitochondrial MAO-B by Pheniprazine [(1-methyl-2-phenylethyl)hydrazine] has been studied. Pheniprazine was shown to behave as a mechanism-based MAO inhibitor. For rat liver MAO-B, the initial non-covalent step was characterized by dissociation constant ( K _i) of 2450 nM and the first-order rate constant ( k _+2) for the covalent adduct formation was 0.16 min^−1. As a reversible inhibitor it was selective towards rat liver MAO-A ( K _i = 420 nM) but the rate of irreversible inhibition of that enzyme was considerably slower ( k _+2 = 0.06 min^−1). MAO-B from ox liver more closely resembled MAO-A from the rat in sensitivity to reversible inhibition by Pheniprazine ( K _i = 450 nm) but it was closer to rat liver MAO-B in rate of irreversible inhibition ( k _+2 = 0.29 min^−1). The K _i values were significantly decreased in the presence of KCN but there was little effect on the k _+2 values. However, sensitivities of the different enzymes to KCN varied widely and considerably higher concentrations of KCN were required for this effect to be apparent with the rat liver mitochondrial MAO-A than with MAO-B from rat and ox liver. The kinetic behaviour of cyanide activation was consistent with partial (non-essential) competitive activation in all cases.
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Some peculiar aspects of monoamine oxidase inhibition.
Neurobiology (Budapest Hungary), 1999Co-Authors: Zakia M. Ben Ramadan, Dostert P, Keith F. TiptonAbstract:: CN- ions enhance the inhibition of monoamine oxidase by the hydrazine derivatives, phenelzine [2-phenylethylhydrazine] and Pheniprazine [(1-methyl-2-phenylethyl)hydrazine]. This involves partial competitive activation of the initial noncovalent enzyme-inhibitor complex with no significant effect on the subsequent reaction to give the irreversibly inhibited species. Whereas the maximum effects on Pheniprazine inhibition of rat liver MAO-B occurred at about 5 microM cyanide, concentrations of 5 mM were necessary for maximum stimulation of MAO-A inhibition. A comparison of the behaviour of rat and ox MAO revealed considerable differences in their sensitivities to Pheniprazine and the potentiating effects of cyanide. Species differences were also evident in the interactions derivatives of milacemide [2-n-pentylaminoacetamide] as substrates and mechanism-based inhibitors of MAO-B. In one case there was evidence for apparently large difference in inhibitor sensitivities between human brain MAO-B from different individuals.
Zakia Ben Ramadan - One of the best experts on this subject based on the ideXlab platform.
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Species Differences in the Selective Inhibition of Monoamine Oxidase (1-methyl-2-phenylethyl)hydrazine and its Potentiation by Cyanide
Neurochemical Research, 2007Co-Authors: Zakia Ben Ramadan, Maria L. Wrang, Keith F. TiptonAbstract:The potentiating effects of cyanide on the inhibition of rat liver mitochondrial monoamine oxidase-A & B and of ox liver mitochondrial MAO-B by Pheniprazine [(1-methyl-2-phenylethyl)hydrazine] has been studied. Pheniprazine was shown to behave as a mechanism-based MAO inhibitor. For rat liver MAO-B, the initial non-covalent step was characterized by dissociation constant ( K _i) of 2450 nM and the first-order rate constant ( k _+2) for the covalent adduct formation was 0.16 min^−1. As a reversible inhibitor it was selective towards rat liver MAO-A ( K _i = 420 nM) but the rate of irreversible inhibition of that enzyme was considerably slower ( k _+2 = 0.06 min^−1). MAO-B from ox liver more closely resembled MAO-A from the rat in sensitivity to reversible inhibition by Pheniprazine ( K _i = 450 nm) but it was closer to rat liver MAO-B in rate of irreversible inhibition ( k _+2 = 0.29 min^−1). The K _i values were significantly decreased in the presence of KCN but there was little effect on the k _+2 values. However, sensitivities of the different enzymes to KCN varied widely and considerably higher concentrations of KCN were required for this effect to be apparent with the rat liver mitochondrial MAO-A than with MAO-B from rat and ox liver. The kinetic behaviour of cyanide activation was consistent with partial (non-essential) competitive activation in all cases.
Svante B. Ross - One of the best experts on this subject based on the ideXlab platform.
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Structural Requirements for Uptake into Serotoninergic Neurones
Pharmacology & Toxicology, 2009Co-Authors: Svante B. RossAbstract:: Experiments were performed to examine whether non-hydroxylated tryptamines and 4-chloroamphetamine utilize the membrane 5-hydroxytryptamine carrier to pass into serotoninergic neurones. The accumulation and deamination of 14C-tryptamine by mouse brain slices or homogenates of rat hypothalamus were not inhibited by cocaine or norzimelidine, a selective inhibitor of the neuronal 5-HT uptake. The prevention by alpha-methyltryptamine (10 mg/kg, intraperitoneally), alpha-ethyltryptamine (20 mg/kg intraperitoneally) and 4-chloroamphetamine (20 mg/kg intraperitoneally) of the irreversible inhibtion of monoamine oxidase by Pheniprazine (2.5 mg/kg intraperitoneally) and clorgyline (5 mg/kg intraperitoneally) in serotoninergic synaptosomes from mouse brain was not antagonized by pretreatment of the animals with norzimelidine (20 mg/kg intraperitoneally). The partial preventing effect of alpha-ethyl-4-methyl-m-tyramine (H 75/12)(2 X 50 mg/kg intraperitoneally) was, on the other hand, antagonized by norzimelidine. These results do not support the hypothesis that non-hydroxylated tryptamines and 4-chloroamphetamine are transported by the 5-HT carrier.
Maria L. Wrang - One of the best experts on this subject based on the ideXlab platform.
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Species Differences in the Selective Inhibition of Monoamine Oxidase (1-methyl-2-phenylethyl)hydrazine and its Potentiation by Cyanide
Neurochemical Research, 2007Co-Authors: Zakia Ben Ramadan, Maria L. Wrang, Keith F. TiptonAbstract:The potentiating effects of cyanide on the inhibition of rat liver mitochondrial monoamine oxidase-A & B and of ox liver mitochondrial MAO-B by Pheniprazine [(1-methyl-2-phenylethyl)hydrazine] has been studied. Pheniprazine was shown to behave as a mechanism-based MAO inhibitor. For rat liver MAO-B, the initial non-covalent step was characterized by dissociation constant ( K _i) of 2450 nM and the first-order rate constant ( k _+2) for the covalent adduct formation was 0.16 min^−1. As a reversible inhibitor it was selective towards rat liver MAO-A ( K _i = 420 nM) but the rate of irreversible inhibition of that enzyme was considerably slower ( k _+2 = 0.06 min^−1). MAO-B from ox liver more closely resembled MAO-A from the rat in sensitivity to reversible inhibition by Pheniprazine ( K _i = 450 nm) but it was closer to rat liver MAO-B in rate of irreversible inhibition ( k _+2 = 0.29 min^−1). The K _i values were significantly decreased in the presence of KCN but there was little effect on the k _+2 values. However, sensitivities of the different enzymes to KCN varied widely and considerably higher concentrations of KCN were required for this effect to be apparent with the rat liver mitochondrial MAO-A than with MAO-B from rat and ox liver. The kinetic behaviour of cyanide activation was consistent with partial (non-essential) competitive activation in all cases.
Feuer G - One of the best experts on this subject based on the ideXlab platform.
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Neuropharmacology of pineal secretions.
Drug metabolism and drug interactions, 1990Co-Authors: Lewis Aj, Kerenyi Na, Feuer GAbstract:: A connection between pineal function and several psychiatric diseases has been shown recently. The diurnal and seasonal rhythmicity of melatonin production is associated with affective disorders and several types of endogenous depression. The cortisolmelatonin ratio was significantly higher in depressed individuals than in healthy controls. Alterations in melatonin secretion may also occur in non-affective psychiatric disorders, such as chronic schizophrenia. Antidepressants and other psychotropic drugs modify melatonin synthesis. In rodents, monoamine oxidase (MAO) inhibitors (e.g. Pheniprazine, harmine or nialamide) increase pineal concentrations of the melatonin precursors, serotonin (5HT) and N-acetyl serotonin (NAS), by enhancing N-acetyl transferase activity. These drugs also increase melatonin, 5HT and NAS in the cerebrospinal fluid. Chronically administered tricyclic antidepressants reduce pineal and serum melatonin content in rodents. In humans, both the MAO-A selective inhibitor clorgyline and the non-selective inhibitor tranylcypromine increase serum melatonin levels. In contrast, serum melatonin remains unaltered by the MAO-B selective inhibitor L-deprenyl. The actions of other drugs on melatonin production, including lithium, propranolol, amphetamine and several monoamine precursors, are in accordance with their psychotropic effects and with their effect on monoamine functions.