Kälviäinen R
Department of Neurology, University Hospital of Kuopio, Finland.
J Intellect Disabil Res. 1998 Dec;42 Suppl 1:63-7.
Tiagabine exerts its antiepileptic drug (AED) activity by selectively inhibiting the uptake of gamma-aminobutyric acid (GABA) onto the transporter molecules, and thus, increasing extracellular concentrations of GABA in the brain. The absorption and elimination of tiagabine follow linear pharmacokinetics. Tiagabine is metabolized by hepatic cytochrome P450 enzymes and enzyme-inducing AEDs increase tiagabine clearance by 50-65%. Tiagabine has shown no clinically important interactions with other drugs, including oral contraceptives. In the perforant pathway stimulation model of status epilepticus, tiagabine reduced the seizure number and severity, and also prevented the loss of pyramidal cells in the hippocampus as well as alleviated impairment of the spatial memory impairment associated with hippocampal damage. Tiagabine has both antiepileptogenic and anticonvulsant effects in the kindling model of epilepsy. Based on the data from the short- and long-term add-on studies, tiagabine is effective adjunctive therapy for all partial seizure types in adolescents and adults. Conversion to tiagabine monotherapy has been also possible in substantial amount of patients with partial seizures in three trials. Tiagabine is generally well-tolerated. The most common adverse events in controlled studies involve the central nervous system; for example, dizziness, asthenia, nervousness, tremor, depressed mood and emotional lability. Special safety analyses with formal neuropsychological testing suggest that tiagabine does not adversely affect cognition or mood. Tiagabine represents an important new therapeutic option for patients with treatment-refractory partial seizures. The role of tiagabine in the management of partial epilepsy of patients with intellectual disability is especially emphasized since tiagabine has a low side-effect profile in the cognitive area.
噻加宾通过选择性抑制γ-氨基丁酸（GABA）向转运分子的摄取来发挥其抗癫痫药物（AED）活性，从而增加大脑中GABA的细胞外浓度。噻加宾的吸收和消除遵循线性药代动力学。噻加宾由肝细胞色素P450酶代谢，酶诱导性抗癫痫药物可使噻加宾的清除率提高50%-65%。噻加宾与其他药物（包括口服避孕药）未显示出具有临床意义的相互作用。在癫痫持续状态的穿通通路刺激模型中，噻加宾减少了癫痫发作的次数和严重程度，还预防了海马体中锥体细胞的丢失，并减轻了与海马体损伤相关的空间记忆损害。在癫痫点燃模型中，噻加宾具有抗癫痫发生和抗惊厥作用。基于短期和长期附加研究的数据，噻加宾是青少年和成人所有部分性癫痫发作类型的有效辅助治疗药物。在三项试验中，相当数量的部分性癫痫患者也有可能转换为噻加宾单药治疗。噻加宾一般耐受性良好。对照研究中最常见的不良事件涉及中枢神经系统；例如，头晕、乏力、紧张、震颤、情绪低落和情绪不稳定。通过正式神经心理学测试进行的特殊安全性分析表明，噻加宾不会对认知或情绪产生不利影响。对于难治性部分性癫痫患者，噻加宾是一种重要的新治疗选择。由于噻加宾在认知领域的副作用较小，因此特别强调了噻加宾在智力残疾患者部分性癫痫管理中的作用。
