title: Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors.
abstract: Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Ankara, Turkey. tuzbay@gata.edu.tr
authors.forename: Tayfun I
authors.initials: TI
authors.lastname: Uzbay
authors.forename: Hakan
authors.initials: H
authors.lastname: Kayir
authors.forename: Mert
authors.initials: M
authors.lastname: Ceyhan
mesh_terms: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D003292:Convulsants / Q000037:antagonists & inhibitors; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D013841:Thiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D003292:Convulsants; D043682:Receptor, Adenosine A1; D013841:Thiazepines; D014970:Xanthines; C050504:tianeptine; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D010433:Pentylenetetrazole