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

• Published in: Biochemical pharmacology 1995-06, Vol.50 (1), p.97-102
• Main Authors: Bondiolotti, Gian Pietro, Galva, Maria Donata, Villa, Federica, Sciaba, Luigi, Picotti, Giovanni B.
• Format: Article
• Language: English
• Subjects: Animals; Benzamides - pharmacology; Biogenic Monoamines - metabolism; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; l-deprenyl; lazabemide; Male; Medical sciences; Miscellaneous; Monoamine Oxidase Inhibitors - pharmacology; monoamine oxidase-B inhibitors; monoamine uptake; Neuropharmacology; Pharmacology. Drug treatments; Picolinic Acids - pharmacology; Rats; Rats, Sprague-Dawley; release; Selegiline - pharmacology; Serotonin - metabolism; synaptosomes; Synaptosomes - metabolism
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)00022-R

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) ⩾ 5-hydroxytryptamine (5 HT) dopamine (DA)). The ic 50 values for lazabemide and Ro 16–6491, respectively, were: 86 μM and 90 μM for NA uptake; 123 μM and 90 μM for 5HT uptake; > 500 μM and > 1000 μM 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 (IC 50 = NA 23 μM, DA 109 μM), and two to three times less potent in inhibiting 5 HT uptake ( ic 50 233 μM). 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 μM) 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.