The effect of amineptine and its two metabolites on monoamine uptake, release and receptor binding was studied in vitro. 2. Amineptine and its two metabolites did not displace labelled ligands for known neurotransmitters and drug receptor sites. 3. Amineptine and its two metabolites did not influence [3H]-5-hydroxytryptamine ([3H]-5-HT) uptake or release by rat brain synaptosomes. Amineptine inhibited [3H]-dopamine and [3H]-noradrenaline ([3H]-NA) accumulation, with IC50 values of 1.4 and 10 μM, respectively. The effect was retained, though with lower efficacy, by the two metabolites. 4. Amineptine released [3H]-dopamine from preloaded synaptosomes. Metabolite 1 had no effect on catecholamine release, and metabolite 2 was about half as active as the parent compound on [3H]-dopamine release. 5. The releasing effect on amineptine on [3H]-dopamine was potentiated by reserpine pretreatment, suggesting that the drug acts on the cytoplasmic neurotransmitter pool. 6. Chronic treatment with amineptine (20 mg kg-1, twice daily for 15 days followed by a 3 days drug withdrawal period) resulted in a decrease of [3H]-spiperone binding sites in striatum, and of [3H]-dihydroalprenolol and [3H]-clonidine in cortex. 7. Chronic treatment with amineptine reduced basal [3H]-dopamine accumulation in striatal synaptosomes, without affecting [3H]-NA or [3H]-5HT accumulation. 8. The adaptive changes in the pre- and postsynaptic dopamine mechanisms observed after long term treatment with amineptine are consistent with the drug acting as an indirect dopamine agonist. 9. The down regulation of β- and α2-noradrenoceptors observed after long term amineptine treatment may play a role in the antidepressant activity of the drug.
|Number of pages||7|
|Journal||British Journal of Pharmacology|
|Publication status||Published - 1986|
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