Tiagabine (hydrochloride)

Tiagabine hydrochloride is an anticonvulsant agent and a selective inhibitor of the GAT-1 GABA transporter with a Ki of ～0.1 μM. Tiagabine hydrochloride potently and selectively inhibits GABA reuptake with IC₅₀s of 67, 446 and 182 nM for ^[3H]GABA uptake in synaptosomes, neurons and glia, respectively. Tiagabine hydrochloride has neuroprotective properties^{[1][2][3][4][5][6][7][8]}. In Vitro:Tiagabine (0.1 μM) hydrochloride inhibits GABA uptake in temporal cortex and white structures from pig brain (50% and 60-68%, respectively)^[2].
Tiagabine (0.1-5 μM) protects neurons against mutant huntingtin (htt)-induced toxicity (withdrawal of Doxycycline (HY-N0565)) in PC12 cells^[4].
Tiagabine (20-100 μM, 1 h) increases viability of SH-SY5Y cells treated with 1 mM MPP^+[5].
Tiagabine (25 min) inhibits [3H]GABA uptake at mouse GAT1 expressed in HEK293 cells, with IC₅₀ of 0.07 μM^[6].
In Vivo:Tiagabine hydrochloride (2-5 mg/kg, i.p., daily) is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's disease, with improving motor performance and attenuating brain atrophy and neurodegeneration^[4].
Tiagabine hydrochloride (5?mg/kg, i.p.) acts as a brake for nigrostriatal microglial activation and reduces dopaminergic neuronal loss in MPTP- and LPS-induced models of PD mice^[5].
Tiagabine hydrochloride shows dose-dependent anti-allodynic effect in a rat model of neuropathic pain (3-30 mg/kg, i.p.) and antinociceptive effects against acute thermal pain in mice (in hot-plate test, 3-10 mg/kg, i.p.)^[7].
Tiagabine (0.5-2 mg/kg, i.p., 21 days) hydrochloride suppresses pentylenetetrazole-induced seizures in mice and improves behavioral and cognitive parameters by modulating BDNF/TrkB expression and neuroinflammatory markers^[8].