Tiagabine hydrochloride hydrate

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)