Some biochemical properties of the new potential antidepressant agent N-methyl-N-propargyl-2-(1-methyl-5-methoxyindolyl)methylamine.
The biochemical properties of the new methyl indole derivative IM-24 (N-methyl-N-propargyl-2(1-methyl-5-methoxyindolyl)methylamine HCl) have been investigated. The activity on both forms of monoamine oxidase MAO was tested in several nervous and non nervous tissues ex vivo after chronic administration. IM-24 is mainly an inhibitor of the activity of MAO A without any effect on intestinal MAO B at the doses studied. IM-24 was compared with tricyclic antidepressants in tests for serotonin (5HT), noradrenaline (NA) and dopamine (DA) uptake inhibition in vitro. IM-24 is mainly an inhibitor of the 5HT uptake mechanism but is less active than paroxetine and chlorimipramine which are very potent 5HT-uptake inhibitors. Radioligand binding techniques in rat brain ex vivo showed that IM-24 after chronic administration (21 days) produces no change in the number or the affinity of the alpha 2-adrenoceptors. IM-24 reduces by 70% the number of 5HT2 receptors but does not modify the affinity for the ligand. IM-24 is thus an interesting compound which combines monoamine oxidase inhibition with inhibition of 5HT uptake. Both these actions will lead to an increase of the availability of serotonin at the synaptic site.
Carranza Gómez-Carpintero
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Department of Research, Laboratorios Morrith, S. A., Madrid, Spain.
Ochoa Estomba
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MC
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D007211:Indoles; D008744:Methylamines; D008996:Monoamine Oxidase Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D011956:Receptors, Cell Surface; D011985:Receptors, Serotonin; C083859:IM 24; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine