Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine uptake inhibitor.
We investigated whether the antidepressant tianeptine shares the dopamine uptake inhibitory properties of the chemically related antidepressant amineptine. Tianeptine dose dependently (5, 10, 20, 40 mg/kg IP) increased locomotor activity in mice. This stimulant effect (20 mg/kg IP) was dose dependently prevented not only by the D1 dopamine receptor antagonist SCH 23390 (7.5. 15, 30 microg/kg SC), but also by the D2 dopamine receptor antagonist haloperidol (50, 100, 200 microg/kg IP), in contrast to that elicited by dopamine uptake inhibitors. Where the latter prevent dexamphetamine-induced (3 mg/kg SC) reversion of akinesia in mice pretreated with reserpine (4 mg/kg SC, 5 h before test), tianeptine (20 mg/kg IP, 30 min before test) did not. Tested up to a concentration of 10-4 M, tianeptine did neither inhibit the [3H]dopamine uptake into mouse striatal synaptosomes nor compete in vitro with the specific binding of [3H]WIN 35,428 at dopamine transporters from striatal membranes. Finally, in mice injected IV with a tracer dose of [3H]WIN 35,428 (1 microCi), the highest tested dose of tianeptine (40 mg/kg IP) did not reduce the specific binding of the radioligand to striatal dopamine transporters. It is concluded that the antidepressant effect of tianeptine does not depend upon a blockade of the neuronal dopamine transporter.
Vaugeois
J M
JM
Unité de Neuropsychopharmacologie Expérimentale, UPRES-A 6036 CNRS, IFRMP, UFR de Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
Corera
A T
AT
Deslandes
A
A
Costentin
J
J
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011869:Radioligand Assay; D013841:Thiazepines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D001552:Benzazepines; D003986:Dibenzocycloheptenes; D018765:Dopamine Uptake Inhibitors; D013841:Thiazepines; C050504:tianeptine; C011597:amineptin; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine