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Effect of long term amineptine treatment on pre‐ and postsynaptic mechanisms in rat brain
Author(s) -
Ceci A.,
Garattini S.,
Gobbi M.,
Mennini T.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb09495.x
Subject(s) - postsynaptic potential , neuroscience , term (time) , chemistry , pharmacology , biology , medicine , receptor , physics , quantum mechanics
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 [ 3 H]‐5‐hydroxytryptamine ([ 3 H]‐5‐HT) uptake or release by rat brain synaptosomes. Amineptine inhibited [ 3 H]‐dopamine and [ 3 H]‐noradrenaline ([ 3 H]‐NA) accumulation, with IC 50 values of 1.4 and 10 μM, respectively. The effect was retained, though with lower efficacy, by the two metabolites. 4 Amineptine released [ 3 H]‐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 [ 3 H]‐dopamine release. 5 The releasing effect of amineptine on [ 3 H]‐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 [ 3 H]‐spiperone binding sites in striatum, and of [ 3 H]‐dihyroalprenolol and [ 3 H]‐clonidine in cortex. 7 Chronic treatment with amineptine reduced basal [ 3 H]‐dopamine accumulation in striatal synaptosomes, without affecting [ 3 H]‐NA or [ 3 H]‐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 α 2 ‐noradrenoceptors observed after long term amineptine treatment may play a role in the antidepressant activity of the drug.