Effect of some monoamine oxidase inhibitors on the thiamin status of rabbits (original) (raw)
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Thiamine is known to have an important role in the protection of different types of cells and tissues against the damage produced by many drugs and toxins. The most important problem limiting the clinical applications of this approach is the poor absorption and bioavailability of thiamine from the sites of administration, a problem which can be solved by the use of the lipid soluble pro-drug for thiamine, benfotiamine. Accordingly, this project was designed to evaluate the serum and tissues availability of thiamine in rats after the administration of single oral dose of benfotiamine compared with that produced by the same oral dose of thiamine, in addition to study the effects of enzyme inducers and inhibitors in this respect utilizing HPLC technique. According to the results obtained in this study one can conclude that thiamine availability after administration of benfotiamine was more in serum, liver, kidney while in the brain more time may be required to reach maximum level.
MAO inhibitors: Risks, benefits, and lore
Cleveland Clinic Journal of Medicine, 2010
Monoamine oxidase (MAO) inhibitors were the first antidepressants introduced, but their use has dwindled because of their reported side effects, their food and drug interactions, and the introduction of other classes of agents. However, interest in MAO inhibitors is reviving. Here, we discuss their use, risks, and benefits in clinical medicine. ■ KEY POINTS Data from multiple studies suggest the efficacy of MAO inhibitors in the management of major depressive disorder and, in particular, major depressive disorder with atypical features and in treatment-resistant depression. When using oral MAO inhibitors, patients must follow a low-tyramine diet to avoid the "cheese reaction," ie, tyramine-induced hypertensive crisis. However, recent studies suggest that traditional dietary advice may be unnecessarily restrictive.
Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology
Frontiers in Pharmacology, 2016
Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong antidepressant efficacy of irreversible MAO inhibitors, their clinical use has been limited by their side effect of potentiation of the cardiovascular effects of dietary amines ("cheese effect"). A number of reversible MAO-A inhibitors which are devoid of cheese effect have been described in the literature, but only one, moclobemide, is currently in clinical use. The irreversible inhibitors of MAO-B, selegiline and rasagiline, are used clinically in treatment of Parkinson's disease, and a recently introduced reversible MAO-B inhibitor, safinamide, has also been found efficacious. Modification of the pharmacokinetic characteristics of selegiline by transdermal administration has led to the development of a new drug form for treatment of depression. The clinical potential of MAO inhibitors together with detailed knowledge of the enzyme's binding site structure should lead to future developments with these drugs.
Metabolic Brain Disease, 2000
Thiamine (T) analogues pyrithiamine, oxythiamine or amprolium in amounts 10-1000 times higher than labelled T, were i.p. injected into rats together with 14 C-T (30 µg; 46.25 KBq). The radioactivity associated with T and its phosphoesters in the plasma and cerebral cortex, brainstem, cerebellum, and sciatic nerve were determined at time intervals from 0.25 to 240 h from injection. The experimental data obtained were processed with a mathematical compartmental model that calculated the fractional rate constants. These are the amount of content in a given compartment that is replaced in 1 h and expressed in per hour. The results showed that all three analogues inhibited thiamine entry from plasma. Instead, oxythiamine enhanced T phosphorylation to T pyrophosphate (TPP); amprolium and oxythiamine enhanced TPP dephosphorylation to monophosphate (TMP); pyrithiamine reduced TPP dephosphorylation and TMP formation, while none of the analogues modified TMP dephosphorylation to T. In conclusion, in living rats, the action of T analogues was much more complex than could be expected from their structure and action in vitro.
The activity of MAO A and B in rat renal cells and tubules
Life Sciences, 1998
The present study reports on the presence of type A and B monoamine oxidase (MAO) activity and their sensitivity to selective MAO-A and MAO-B inhibition by Ro 41-1049 and lazabemide, respectively, in homogenates of isolated rat renal tubules. Non-linear analysis of the saturation curve of H-5-hydroxytryptamine (3H-5-HT ) deamination revealed a Km of 351+/-71 microM (n=4) and a Vmax of 25+/-2 nmol mg protein(-1) h(-1). Deamination of 14C-beta-phenylethylamine (14C-beta-PEA) was also a saturable process yielding Km values of 58+/-12 microM and Vmax values of 24+/-2 nmol mg protein(-1) h(-1). Ro 41-1049 produced a concentration-dependent inhibition of 3H-5-HT deamination with a Ki of 24 nM. Deamination of 14C-beta-PEA was found to be reduced by lazabemide in a concentration-dependent manner with a Ki value of 17 nM. The effect of these selective MAO inhibitors on dopamine fate and DOPAC formation in isolated tubular epithelial cells was also studied. In these studies a clear inhibition of DOPAC formation was observed with Ro 41-1049 (250 nM), while 250 nM lazabemide was found not to increase the accumulation of newly-formed DA in those tubular epithelial cells loaded with 50 microM L-DOPA. In conclusion, the results presented here confirm the presence of both MAO-A and MAO-B activity in renal tubular epithelial cells, that MAO-A is the predominant enzyme involved in the deamination of the natriuretic hormone dopamine and that the deamination of newly-formed dopamine is a time-dependent process which occurs early after the decarboxylation of L-DOPA.
A monoamine oxidase inhibitor in human urine
Biochemical Pharmacology, 1980
Enzyme inhibitors may be useful as drugs FT. Although some endogenous enzyme inhibitors are well recognised, e.g. of dopamine B-hydroxylase [Z], their possible in tivo roles as physiological regulators of enzyme activity have been little studied. Following an earlier and as yet unconfirmed report [3] that plasma from schizophrenics with low platelet monoamine oxidase (MAO) (EC 1.4.3.4.) activity contains an MAO inhibitor not demonstrable in normal plasma, we have been able to demonstrate that normal human urine contains an inhibitor or inhibitors of both MAO A and 6, and that this inhibition cannot be accounted for by the activity of the quantitatively main urinary constituents or by a large group of known monoamine substrates or metabolites. The inhibitor was assayed by its effect on rat liver MAO. Except where specified otherwise, the test system contained 100 J,I~ of 0.1 M sodium phosphate buffer, pH 7.4, 20 ul rat liver homogenate (2.5% w/v), 20 ~1 14C-tyramine (150 yM, sp.act. 2.5 ~Ci/~~le~ and 100 ~1 of urine, or potential inhibitory substances diluted in buffer or of buffer alone. The mixture was incubated at 37'C for 30 min, the reaction stopped with 0.1 ml of 2 M citric acid and the reaction products extracted into 3 ml toluene/ethyl acetate (1:l). A similar system was used with '"C-5-hydroxytryptamine (5-HT) (sp.act. 2.5 uCi/umole) but when "'C-phenylethylamine (PEA) (sp.act. 12.5 ~C~/~mole) was used as substrate, 3 ml toluene alone was employed. Radioactive substances were obtained from the Radiochemical Centre, Amersham. Assays were carried out in duplicate, using reagents of analytical grade, from British Drug Houses (Poole, U.K.) or Sigma London Chemical Co.Ltd. (Kingston-upon-Thames. U.K.). All the human urine samples (random specimens from 14 normal subjects) tested showed varying degrees of inhibition ranging from 25-75%, with a mean of 49% f 7.1 (mean * S.D.), The degree of inhibition was similar when the pH of the urine was adjusted to pH 7.4, and whether a flocculent or clear portion of urine was tested. Human platelet (1 mg protein/ml) MAO was inhibited to a similar extent by the various samples, so that the effect does not depend on the generation of an inhibitor by rat liver. Constituent Cont. % Inhibition Constituent Cont. % Inhibition (mg/lOOml) (mg/lOOml) Urea 2000 4 Glycine 44 0
Anorexia and antagonism of thiamin utilization in poultry treated with furazolidone
Quarterly journal of experimental physiology (Cambridge, England), 1982
Furazolidone (0.4% w/w in the feed, 10 days) reduced the feed intake and growth in 9 week old chickens, and increased the amount of 5-hydroxytryptamine (5-HT) in the brain. The drug also increased the stimulation of transketolase activity by thiamine pyrophosphate (TPP) in lysed blood cells (TPP effect), and the concentrations of pyruvate and lactate in the blood. Experiments with pair-fed birds showed that the reduction in feed intake in furazolidone-treated chickens could account for the reduced growth. The drug also produced anorexia in ducklings and turkey poults. In chickens, the anorectic action of furazolidone was unaffected by methergoline (1 mg/kg, twice daily, I.M), and in ducklings furazolidone did not consistently produce anorexia, although it always inhibited monoamine oxidase (MAO) activity in the brain. These observations suggest that the anorectic action of the drug was not tryptaminergic in nature. The increase in the TPP effect found in preparations from furazolido...
Lesion-induced reductions in trace amine accumulation: Dependence on MAO inhibitor pretreatment
Brain Research Bulletin, 1989
NGUYEN, T. V., A. V. JUORIO AND A. J. GREENSHAW. Lesion-induced reductions in trace amine accumulation: Dependence on MAO inhibitor pretreatment.BRAIN RES BULL 22(2) 197-200, 1989.-Striatal amine levels were measured six weeks tier unilateral injections of 6-OHDA (8 pg) into the substantia nigra in male Wistar rats pretreated with monoamine oxidase inhibitors. After (-) deprenyl.HCl pretreatment (2 mgkg-1 SC 2 hr), p-phenylethylamine,