Summary
The effects of amineptine on3H-dopamine uptake and 14C-dopamine release have been studied simultaneously in double labelling test performed on rat striatal synaptosomes.3H-dopamine uptake was completely inhibited at 10μM amineptine, a concentration which produced only a weak 14C-DA release (13% of the 14C-radioactivity stored). The IC 50 for the inhibition of3H-DA uptake was not modified by a previous treatment with reserpine whereas the IC 50 of (+) amphetamine and the IC 50 of clomipramine were decreased 9 fold and increased two fold, respectively. In binding studies on rat striatal membranes amineptine displacesin vitro the3H-GBR 12783, bound specifically to a component of the neuronal DA uptake complex. The apparent affinity of amineptine for this binding site was more than 150 times higher than its affinity for the binding site of3H-desipramine on rat cortical membranes. In mice, increasing doses of amineptine injected i. p. reduced in a dose dependent manner the specific retention of radioactivity in the striatum after an i. v. injection of a tracer dose of3H-GBR 12783. These data indicate that amineptine inhibits DA uptake and is virtually devoid of DA releasing effects. It displays a relatively low affinity for the NE uptake system. Its neurochemical profile in the double labelling test clearly differs from that of (+) amphetamine and from that of classical tricyclic anti-depressants.
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Bonnet J-J, Lemasson M-H, Costentin J (1984) Simultaneous evaluation by a double labelling method of drug-induced uptake inhibition and release of dopamine in synaptosomal preparation of rat striatum. Biochem Pharmac 33: 2129–2136
Bonnet J-J, Costentin J (1986 a) GBR 12783, a potent and selective inhibitor of dopamine uptake: biochemical studiesin vivo andex vivo. Eur J Pharmacol 121: 199–209
Bonnet J-J, Dubuc I, Costentin J (1986 b) Effects of antidepressant drugs on uptake and storage of3H-dopamine by rat striatal vesicles. In: Woodruff GN, Poat JA, Roberts PJ (eds) Dopaminergic systems and their regulation, Macmillan, pp 401–402
Bonnet J-J, Protais P, Chagraoui A, Costentin J (1986 c) High-affinity3H-GBR 12783 binding to a specific site associated with the neuronal dopamine uptake complex in the central nervous system. Eur J Pharmacol 126: 211–222
Chagraoui A, Bonnet J-J, Protais P, Costentin J (submitted)In vivo binding of3H-GBR 12783, a selective dopamine uptake inhibitor, in mouse striatum. Neurosci Lett
Jenner P, Marsden CD (1982) The mode of action of sulpiride as an atypical antidepressant agent. In: Typical and atypical antidepressants. Raven Press, New York, pp 85–103
Kamiya H, Takano Y, Sakurai Y, Saito R, Kohjimoto Y (1981) Effect of imipramine on high potassium evoked3H-dopamine release in the rat striatum. Res Comm Chem Path Pharmac 30: 49–60
Koe BK (1976) Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J Pharmacol Exp Ther 199: 649–661
Lemasson M-H, Bonnet J-J, Costentin J (1984) Artefactual inhibition of dopamine uptake by psychotropic drugs on striatal synaptosomal preparation. Biochem Pharmac 33: 2137–2141
Masuoka DT, Alcaraz AF, Schott HF (1982)3H-dopamine release by damphetamine from striatal synaptosomes of reserpinized rats. Biochem Pharmacol 31: 1969–1974
Offermeier J, Potgieter B, Du Preez HG, Meiring PJ (1977) Studies of the pharmacology of a new antidepressant S 1694. S Afr Med J 51: 62–66
Raisman R, Sette M, Pimoule C, Briley M, Langer SZ (1982) High-affinity3H-desipramine binding in the peripheral and central nervous system: a specific site associated with the neuronal uptake of noradrenaline. Eur J Pharmacol 78: 345–351
Randrup A, Braestrup C (1977) Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression. Psychopharmacology 53: 309–314
Rehavi M, Skolnick P, Brownstein MJ, Paul SM (1982) High affinity binding of3H-desipramine to rat brain: a presynaptic marker for noradrenergic uptake sites. J Neurochem 38: 889–895
Ross SB, Kelder D (1979) Inhibition of3H-dopamine accumulation in reserpinized and normal rat striatum. Acta Pharmacol Toxicol 44: 329–335
Van der Zee P, Koger HS, Gootjes J, Hespe W (1980) Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur J Med Chem 15: 363–370
Willner P (1983) Dopamine and depression: review of recent evidences. III — The effects of antidepressant treatments. Brain Res Rev 6: 237–246
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Bonnet, J.J., Chagraoui, A., Protais, P. et al. Interactions of amineptine with the neuronal dopamine uptake system: Neurochemicalin vitro andin vivo studies. J. Neural Transmission 69, 211–220 (1987). https://doi.org/10.1007/BF01244342
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DOI: https://doi.org/10.1007/BF01244342