Anticonvulsant active inhibitor of GABA transporter subtype 1, tiagabine, with activity in mouse models of anxiety, pain and depression.
BACKGROUND
Tiagabine, a selective inhibitor of GABA transporter subtype 1 is used as an add-on therapy of partial seizures in humans but its mechanism of action suggests other potential medical indications for this drug. In this research we assess its pharmacological activity in several screening models of seizures, pain, anxiety and depression in mice.


METHODS
For pharmacological tests tiagabine was administered intraperitoneally 60 min before the assay. Behavioral tests were performed using models of chemically and electrically induced seizures, thermal acute pain and formalin-induced tonic pain. Anxiolytic-like properties were evaluated using the four plate test and the elevated plus maze test. Antidepressant-like activity was assessed in the forced swim test. In addition, to exclude false positive results in these assays, the influence of tiagabine on animals' locomotor activity and motor coordination was investigated, too.


RESULTS
Tiagabine demonstrated anticonvulsant properties in chemically induced seizures (pentylenetetrazole and pilocarpine seizures). At the dose of 100mg/kg it also elevated the seizure threshold for electrically induced seizures by 31.6% (p<0.01), but it had no activity in the maximal electroshock seizure test. Tiagabine showed anxiolytic-like and antidepressant-like effects. Although it apparently reduced animals' nociceptive responses in pain tests, these activities rather resulted from its sedative and motor-impairing properties demonstrated in the locomotor activity and the rotarod tests, respectively.


CONCLUSIONS
The results obtained in the present study suggest that tiagabine, apart its anticonvulsant effect, has anxiolytic-like, sedative and antidepressant-like properties. In view of this, it can be potentially used in the treatment of anxiety and mood disorders.
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: salat.kinga@gmail.com.
Kinga
K
Sałat
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Adrian
A
Podkowa
Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Jagiellonian University, Medical College, Kraków, Poland.
Paula
P
Kowalczyk
Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Jagiellonian University, Medical College, Kraków, Poland.
Katarzyna
K
Kulig
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Anna
A
Dziubina
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Barbara
B
Filipek
Department of Radioligands, Jagiellonian University, Medical College, Kraków, Poland.
Tadeusz
T
Librowski
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D050485:GABA Plasma Membrane Transport Proteins; D008297:Male; D051379:Mice; D009557:Nipecotic Acids / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000523:psychology; D012640:Seizures / Q000188:drug therapy / Q000523:psychology; D000078308:Tiagabine
D000927:Anticonvulsants; D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; D000078308:Tiagabine
GABA re-uptake; Mouse models of seizures, pain and mood disorders; Plasma membrane GABA transporter subtype 1; Tiagabine