n-(2-aminoethyl)-4-chlorobenzamide-hydrochloride has been researched along with lazabemide* in 4 studies
4 other study(ies) available for n-(2-aminoethyl)-4-chlorobenzamide-hydrochloride and lazabemide
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In vitro effects on monoamine uptake and release by the reversible monoamine oxidase-B inhibitors lazabemide and N-(2-aminoethyl)-p-chlorobenzamide: a comparison with L-deprenyl.
To investigate whether the reversible monoamine oxidase-B (MAO-B) inhibitors lazabemide and Ro 16-6491 have any additional effect on monoamine uptake and release, in vitro experiments were performed on rat forebrain synaptosomes and blood platelets. The effects of the two drugs were compared with those of L-deprenyl, the well-known irreversible MAO-B inhibitor which is reported to affect amine uptake. Both lazabemide and Ro 16-6491 behaved as weak inhibitors of [3H]monoamine uptake by synaptosomes, with a similar rank order of potency for amine uptake inhibition (noradrenaline (NA) > or = 5-hydroxytryptamine (5 HT) > dopamine (DA)). The IC50 values for lazabemide and Ro 16-6491, respectively, were: 86 microM and 90 microM for NA uptake; 123 microM and 90 microM for 5HT uptake; > 500 microM and > 1000 microM for DA uptake. L-Deprenyl (rank order of inhibitory potency: NA > DA > 5 HT) was four to 10 times more potent than either compound in inhibiting [3H]catecholamine uptake (IC50 = NA 23 microM, DA 109 microM), and two to three times less potent in inhibiting 5 HT uptake (IC50 233 microM). Lazabemide and Ro 16-6491 also differed from L-deprenyl in their ability to induce release of endogenous monoamines from synaptosomes. Thus, Ro 16-6491 (500 microM) induced a greater 5 HT release than did L-deprenyl, but was less effective than L-deprenyl in releasing DA. On the contrary, lazabemide was almost completely inactive on either 5 HT and DA release. The differential effect of the three MAO-B inhibitors on synaptosome 5 HT uptake and release was confirmed by [14C]5HT uptake and liberation experiments with isolated rat platelets. The data indicate that the reversible MAO-B inhibitors lazabemide and Ro 16-6491 at relatively high concentrations possess amine uptake-inhibiting properties. With regard to the effects examined, lazabemide markedly differs from L-deprenyl since it does not interfere with DA uptake nor induce amine release from synaptosomes. Topics: Animals; Benzamides; Biogenic Monoamines; Blood Platelets; Male; Monoamine Oxidase Inhibitors; Picolinic Acids; Rats; Rats, Sprague-Dawley; Selegiline; Serotonin; Synaptosomes | 1995 |
Monoamine oxidase inhibition by moclobemide and 2-amino-ethyl carboxamide derivatives: mode of action and kinetic characteristics.
The selective, reversible inhibitors of monoamine oxidase (MAO) moclobemide and Ro 41-1049 (selective for MAO-A), as well as of Ro 16-6491 and Ro 19-6327 (selective for MAO-B) inhibited the enzyme with an initial competitive phase, followed by a time-dependent inhibition of MAO. Ro 41-1049, Ro 16-6491 and Ro 19-6327, being activated by MAO into reversible adducts, fit into the classification as mechanism-based inhibitors. Conversely, since no product formation was observed after incubation of tissue homogenates with moclobemide, this drug probably belongs to the class of the "slow-binding" MAO inhibitors. Topics: Animals; Benzamides; Blood Platelets; Brain; Cell Membrane; Female; Humans; In Vitro Techniques; Kinetics; Moclobemide; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Picolinic Acids; Placenta; Pregnancy; Rats; Thiazoles | 1990 |
[3H]Ro 19-6327: a reversible ligand and affinity labelling probe for monoamine oxidase-B.
This study demonstrated the existence of specific binding sites for [3H]Ro 19-6327 in human platelet membranes. This compound is a novel, time-dependent inhibitor of monoamine oxidase type B (MAO-B) and is structurally closely related to [3H]Ro 16-6491. The density of the sites labelled with high affinity by [3H]Ro 19-6327 was similar to that observed in previous studies with [3H]Ro 16-6491 as ligand. Binding was reversible at 20 degrees C and showed a relatively slow dissociation (t1/2 = 220 min). The dissociation rate was markedly decreased (t1/2 = greater than 24h) at 0 degrees C. MAO-B, but not MAO-A inhibitors, effectively prevented the binding of [3H]Ro 19-6327. Like [3H]Ro 16-6491, [3H]Ro 19-6327 is recognized as a substrate by MAO-B, being eventually deaminated by the enzyme. Since the deaminated aldehyde derivative of Ro 19-6327 did not inhibit MAO-B, a still unidentified reversible adduct, formed at the MAO-B active site, might explain the high potency and selectivity of [3H]Ro 19-6327. Incubation of the radioligand-enzyme complex from platelet and brain membranes with NaBH3CN and acetic acid (to pH 4.5) caused the irreversible incorporation of the radioactivity into a single polypeptide as shown by SDS-PAGE analysis. This polypeptide had a molecular weight identical to that of the MAO-B subunit, i.e. 58,000. The presence of unlabelled MAO-B inhibitors in the incubation mixture prevented the covalent incorporation of [3H]Ro 19-6327. The irreversible MAO-B inhibitor, [3H] pargyline, labelled a protein with a molecular weight identical to the protein labelled by [3H]Ro 19-6327.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Affinity Labels; Benzamides; Blood Platelets; Brain; Cell Membrane; Electrophoresis, Polyacrylamide Gel; Humans; In Vitro Techniques; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Nerve Tissue Proteins; Picolinic Acids | 1989 |
Interactions of the novel inhibitors of MAO-B Ro 19-6327 and Ro 16-6491 with the active site of the enzyme.
Topics: Affinity Labels; Animals; Benzamides; Binding Sites; Humans; In Vitro Techniques; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Picolinic Acids | 1988 |