Tiagabine is an inhibitor of GABA transporter 1 (GAT-1; IC50 = 49 nM for GAT-1 expressed in CHO cells).1 It inhibits seizures induced by DMCM in mice (ED50 = 1.2 mg/kg, i.p.).2 Tiagabine reduces allodynia in a rodent model of neuropathic pain when used at a dose of 72.8 ?mol/kg, and it acts synergistically with gabapentin to delay pain responses in mice in the hot plate test.3,4 Formulations containing tiagabine have been used as adjunctive therapies in the treatment of partial seizures.
1.Nakada, K., Yoshikawa, M., Ide, S., et al.Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transportsBioorg. Med. Chem.21(17)4938-4950(2013) 2.Andersen, K.E., Braestrup, C., Gr?nwald, F.C., et al.The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidateJ. Med. Chem.36(12)1716-1725(1993) 3.Giardina, W.J., Decker, M.W., Porsolt, R.D., et al.An evaluation of the GABA uptake blocker tiagabine in animal models of neuropathic and nociceptive painDrug Dev. Res.44(2-3)106-113(1998) 4.?uszczki, J.J., Ko?acz, A., Wojda, E., et al.Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: An isobolographic analysisPharmacol. Rep.61(3)459-467(2009)