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Latest publication 06/01/2015

Anticonvulsant active inhibitor of GABA transporter subtype 1- tiagabine- with a

Background Tiagabine, a selective inhibitor of GABA transporter subtype 1 is used as an add-on therapy of partial seizures in humans but its...

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    [title] => Anticonvulsant active inhibitor of GABA transporter subtype 1- tiagabine- with a
    [paragraph] => Anticonvulsant active inhibitor of GABA transporter subtype 1, tiagabine, with activity in mouse models of anxiety, pain and depression
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Authors
Kinga Sa?ata, Adrian Podkowaa, Paula Kowalczykb, Katarzyna Kuligb, Anna Dziubinaa, Barbara Filipeka, Tadeusz Librowskic

 Lab
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland
Journal
Pharmacological Reports
Abstract
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 100 mg/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.
BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830)
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