Effect of long term amineptine treatment on pre‐ and postsynaptic mechanisms in rat brain
Open Access
- 1 May 1986
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 88 (1), 269-275
- https://doi.org/10.1111/j.1476-5381.1986.tb09495.x
Abstract
1 The effect of amineptine and its two metabolites on monoamine uptake, release and receptor binding was studied in vitro. 2 Amineptine and its two metabolities did not displace labelled ligands for known neurotransmitters and drug receptor sites. 3 Amineptine and its two metabolities 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 of 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]-dihyroalprenolol and [3H]-clonidine in cortex. 7 Chronic treatment with amineptine reduced basal [3H]-dopamine accumulation in striatal synaptosomes, without affecting [3H]-NA or [3H]-5-HT 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.This publication has 27 references indexed in Scilit:
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