Search results for "monoamine oxidase inhibitors"
showing 10 items of 17 documents
The neuronal efflux of noradrenaline: Dependency on sodium and facilitation by ouabain
1974
Rabbit hearts were isolated after pretreatment with the MAO inhibitor pargyline and with reserpine and were perfused with 200 ng/ml noradrenaline for 1 h. During the subsequent wash-out with an amine-free solution for 2 h, the neuronal efflux of noradrenaline declined mono-exponentially with a mean halftime of 42 min. Both Na+-free solution and ouabain caused facilitation of the efflux which thereafter declined in a multi-exponential fashion. The maximum facilitation was reached after 3 min of Na+-free perfusion and 25 min after introduction of ouabain. The amount of exogenous noradrenaline accumulated in the heart was only partially released when the extracellular Na+-concentration was nor…
Release of endogenous 3,4-dihydroxyphenylethylamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland. Effects …
1986
: Isolated rat neurointermediate lobes were incubated in vitro. The release of 3,4-dihydroxyphenylethylamine (dopamine, DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and methoxyphenylethanol (MOPET) was determined by HPLC with electrochemical detection. Under resting conditions, the outflow of metabolites was 35–50 times that of DA. HVA accounted for 50%, DOPAC for 45%, and MOPET for 5% of the metabolites. Although an equivalent of 40–50% of the tissue DA content was released per hour as metabolites, the tissue DA content was not reduced after 110 min of incubation. The spontaneous outflow of DA and its metabolites was not affected by the DA uptake inhibitor GBR 12921 (1…
Inhibition of dextromethorphan metabolism by moclobemide.
1998
This pilot study was conducted to evaluate the potential of the new antidepressant moclobemide to inhibit the cytochrome enzyme P4502D6 (CYP2D6) using the cough suppressant dextromethorphan as a substrate in four extensive metabolizers (EM) of debrisoquine. The subjects received seven oral doses of 20 mg dextromethorphan at 4-h intervals over 2 days (1 and 2) and subsequently moclobemide (300 mg b.i.d.) for 9 days. On days 10 and 11, they received seven doses of 20 mg dextromethorphan in addition to moclobemide. During monotreatment and combined treatment, blood was collected on days 2 and 11, respectively, for determination of dextromethorphan and its demethylated metabolites using automat…
Effects of moclobemide on sexual performance and nocturnal erections in psychogenic erectile dysfunction
2001
Rationale and objectives: We tested the hypothesis that the selective reversible MAO-A inhibitor moclobemide has a specific therapeutic effect on erectile dysfunction independent of its antidepressive properties. Methods: In a double-blind placebo controlled study, 12 male outpatients suffering from psychogenic erectile dysfunction without any other psychiatric disorder were investigated. Based on comprehensive diagnosis before the beginning of the study, organic factors relevant for sexual function were excluded. The treatment period was 8 weeks. Half the patients received 450 mg moclobemide during the first week, and 600 mg afterwards; the others received placebo. Apart from assessment of…
Monoamine Oxidase Inhibition by β-Carbolines: A Quantum Chemical Approach
1979
Monoamine oxidase inhibition by beta-carboline derivatives is related to the energy change, delta E, arising from complex formation between the inhibitor and the enzyme. The energy change was expressed in terms of electronic indexes, which were estimated for a set of aromatic beta-carbolines. The electronic indexes were correlated to the experimental activity indexes by a simplified quantum chemical perturbational treatment with a multiple regression procedure. A characteristic structure for the inhibitor-enzyme complex was derived from the correlation. The molecules are linked by two kinds of bond. One involves the lone pyridine nitrogen pair of beta-carbolines; the other is due to a pi-el…
The Anticonvulsant FCE 26743 is a Selective and Short-acting MAO-B Inhibitor Devoid of Inducing Properties towards Cytochrome P450-dependent Testoste…
1994
Abstract The effects of the potent anticonvulsant FCE 26743 ((S)-2-(4-(3-fluorobenzyloxy)benzylamino)propionamide) on monoamine oxidase (MAO) activity were measured in-vitro and ex-vivo using rat tissue homogenates. In-vitro, FCE 26743 showed potent and selective inhibitory properties towards liver MAO-B, with IC50 values about 10−7 m for MAO-B and higher than 10−5 m for MAO-A. When determined ex-vivo in brain, the ED50 value for the inhibition of MAO-B was 1·1 mg kg−1 (p.o.) 1 h post-dosing, whereas MAO-A remained virtually unaffected after administration of 60 mg kg−1. Similar effects were seen in liver. Following oral administration of 5 mg kg−1 FCE 26743 to rats, brain MAO-B inhibitio…
Novel Hydrazine Molecules as Tools To Understand the Flexibility of Vascular Adhesion Protein-1 Ligand-Binding Site: Toward More Selective Inhibitors
2011
Vascular adhesion protein-1 (VAP-1) belongs to a family of amine oxidases. It plays a role in leukocyte trafficking and in amine compound metabolism. VAP-1 is linked to various diseases, such as Alzheimer's disease, psoriasis, depression, diabetes, and obesity. Accordingly, selective inhibitors of VAP-1 could potentially be used to treat those diseases. In this study, eight novel VAP-1 hydrazine derivatives were synthesized and their VAP-1 and monoamine oxidase (MAO) inhibition ability was determined in vitro. MD simulations of VAP-1 with these new molecules reveal that the VAP-1 ligand-binding pocket is flexible and capable of fitting substantially larger ligands than was previously believ…
Antidepressant drugs and memory: Insights from animal studies
2007
This is a selective review of the literature concerning the effects of antidepressant drugs on animal memory, which was performed with the aid of the PubMed database. Monoamine oxidase inhibitors tend to either have no effect on memory or result in its improvement. Studies with cyclic antidepressants have reported no effect or, more often, memory impairments. Pre-training administration of selective serotonin reuptake inhibitors (SSRIs) has been shown to have either no effect on memory or undermine it (with some isolated exceptions, in which improvements have been recorded), while post-training administration of SSRIs has been demonstrated to improve memory or have no effect. A small group …
Effects of brofaremine (CGP 11 305A), a short-acting, reversible, and selective inhibitor of MAO-A on sleep, nocturnal penile tumescence and nocturna…
1987
The effects of brofaremine (CGP 11 305A), a short-acting, reversible and selective inhibitor of MAO-A, on sleep, nocturnal penile tumescence (NPT) and hormonal secretion during the night were studied during a long-term trial. Three healthy males underwent sleep-EEG and NPT recordings during consecutive nights (1) under placebo, (2) under stepwise increasing dosages of brofaremine and (3) under placebo after withdrawal. Hormone profiles were sampled during selected nights to analyze the plasma concentration of cortisol, HGH, prolactin, testosterone, LH and FSH. REM sleep was suppressed markedly under 150 mg brofaremine, while stages 1 and 2 increased. In comparison to the effect of irreversi…
The role of cytochrome P450 2D6 in the metabolism of moclobemide.
1996
The metabolic fate of moclobemide (Ro 11-1163), a new reversible and selective inhibitor of monoamine oxidase type A (MAO-A), has been assessed in a pilot study in 2 debrisoquine poor metabolizers (PM) and 4 extensive metabolizers (EM) after multiple oral dosings of moclobemide with and without co-medication of dextromethorphan. Absorption and disposition parameters were not different between PM and EM. Concurrent application of dextromethorphan, a selective substrate of CYP2D6, did not affect the pharmacokinetics of moclobemide. These results indicate that the cytochromal isoenzyme CYP2D6 does not play a major role in the metabolic degradation of moclobemide. Limited CYP2D6 activities beca…