Sałat Kinga, Podkowa Adrian, Kowalczyk Paula, Kulig Katarzyna, Dziubina Anna, Filipek Barbara, Librowski Tadeusz
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Pharmacol Rep. 2015 Jun;67(3):465-72. doi: 10.1016/j.pharep.2014.11.003. Epub 2014 Nov 21.
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.
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.
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.
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.
噻加宾是γ-氨基丁酸转运体1亚型的选择性抑制剂，在人类中用作部分性癫痫的附加治疗药物，但其作用机制提示该药物可能还有其他潜在的医学适应症。在本研究中，我们评估了其在小鼠癫痫、疼痛、焦虑和抑郁的多种筛选模型中的药理活性。
进行药理测试时，在实验前60分钟腹腔注射噻加宾。使用化学和电诱导癫痫、热急性疼痛和福尔马林诱导的强直性疼痛模型进行行为测试。使用四板试验和高架十字迷宫试验评估抗焦虑样特性。在强迫游泳试验中评估抗抑郁样活性。此外，为了排除这些试验中的假阳性结果，并研究了噻加宾对动物运动活性和运动协调性的影响。
噻加宾在化学诱导的癫痫（戊四氮和毛果芸香碱癫痫）中表现出抗惊厥特性。在100mg/kg剂量下，它还使电诱导癫痫的发作阈值提高了31.6%（p<0.01），但在最大电休克癫痫试验中没有活性。噻加宾显示出抗焦虑样和抗抑郁样作用。虽然它在疼痛测试中明显降低了动物的伤害性反应，但这些活性分别是由其在运动活性试验和转棒试验中表现出促镇静和运动损害特性导致的。
本研究获得的结果表明，噻加宾除了具有抗惊厥作用外，还具有抗焦虑样、镇静和抗抑郁样特性。鉴于此，它可能潜在地用于治疗焦虑和情绪障碍。
