Co-administration of gamma-vinyl GABA and cocaine: preclinical assessment of safety.
Co-administration of gamma-vinyl GABA and cocaine: preclinical assessment of safety.
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γ-乙烯基 GABA 和可卡因的共同给药：临床前安全性评估。
DOI：
10.1016/s0024-3205(99)00351-3
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发表时间：
1999
期刊：
影响因子：
6.1
通讯作者：
Abumrad,N
中科院分区：
文献类型：
--
作者：
Molina,PE;Ahmed,N;Ajmal,M;Dewey,S;Volkow,N;Fowler,J;Abumrad,N
γ-乙烯基 GABA（GVG，氨己烯酸）是一种不可逆的 GABA 转氨酶 (GABA-T) 抑制剂，可抑制可卡因诱导的位置偏好和自我给药，已被提议作为可卡因成瘾的治疗方法。因此，评估 GVG 与可卡因的组合是否会增强毒性非常重要。单独施用GVG（60mg/kg IV）（n=8）或与可卡因（5mg/kg IV）联合施用（n=6）没有观察到死亡。可卡因引起的心电图改变不受 GVG 预处理的影响。 GVG 治疗可降低血浆丙氨酸氨基转移酶活性，并且可卡因给药不会进一步改变这种情况。这些结果表明，GVG 和可卡因的急性联合给药不会立即导致足够显着的心血管或肝脏毒性，从而排除进一步的临床试验。
Gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of GABA transaminase (GABA-T) that inhibits cocaine-induced place preference and self administration has been proposed as a treatment for cocaine addiction. It was therefore important to assess if there was an enhanced toxicity from the combination of GVG with cocaine. No mortality was observed with administration of GVG (60 mg/kg IV) alone (n=8) or in combination (n=6) with cocaine (5 mg/kg IV). Cocaine-induced EKG alterations were not affected by GVG pretreatment. Plasma alanine amino transferase activity was reduced by GVG treatment and this was not further modified by cocaine administration. These results suggest that acute co-administration of GVG and cocaine does not result in immediate cardiovascular or hepatic toxicity of sufficient significance, to preclude further clinical trials.