氨己烯酸对γ-氨基丁酸（GABA）系统影响的实验研究。
Experimental studies of the influence of vigabatrin on the GABA system.
作者信息
Gram L, Larsson O M, Johnsen A, Schousboe A
机构信息
University Clinic of Neurology, Hvidovre Hospital, Copenhagen, Denmark.
出版信息
Br J Clin Pharmacol. 1989;27 Suppl 1(Suppl 1):13S-17S. doi: 10.1111/j.1365-2125.1989.tb03455.x.
Abstract
- Studies of the influence of clinically relevant concentrations of vigabatrin on GABA-transaminase and on the release of endogenous GABA were performed in selectively cultured astrocytes and neurons. In addition, the two stereoisomers of vigabatrin were investigated separately. 2. The results indicated a preferential inhibition of neuronal GABA-transaminase by vigabatrin. 3. Only the (S)-form of vigabatrin seems to inhibit GABA-transaminase. This finding corresponds to observations in epileptic animals that the (R)-form exhibits no anticonvulsant effect. 4. Resynthesis of GABA-transaminase, following withdrawal of vigabatrin showed that maximum enzyme activity was obtained within 6 days. This finding corresponds to the persistent effect after withdrawal of the drug in patients, observed in clinical trials. 5. At a concentration of 25 microM, vigabatrin caused a significant increase in the release of endogenous GABA from cultured GABAergic neurons. Although no data on brain levels of the drugs are currently available, judging from vigabatrin blood concentrations in man and from information of brain levels in animals, following chronic treatment, it is conceivable that a sufficiently high concentration of the drug in human brain is obtained to augment GABA release.
摘要
- 在选择性培养的星形胶质细胞和神经元中，研究了临床相关浓度的氨己烯酸对γ-氨基丁酸转氨酶（GABA-转氨酶）及内源性GABA释放的影响。此外，还分别对氨己烯酸的两种立体异构体进行了研究。2. 结果表明，氨己烯酸对神经元GABA-转氨酶有优先抑制作用。3. 似乎只有氨己烯酸的（S）-型能抑制GABA-转氨酶。这一发现与在癫痫动物中的观察结果相符，即（R）-型没有抗惊厥作用。4. 停用氨己烯酸后GABA-转氨酶的重新合成表明，在6天内可获得最大酶活性。这一发现与临床试验中观察到的患者停药后药物的持续作用相符。5. 在浓度为25微摩尔时，氨己烯酸使培养的GABA能神经元释放的内源性GABA显著增加。虽然目前尚无关于药物脑内水平的数据，但从人体氨己烯酸血药浓度以及动物脑内水平信息判断，长期治疗后，人脑有可能获得足够高浓度的药物以增加GABA释放。
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本文引用的文献
1
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75.
2
The action of gamma-vinyl-GABA and gamma-acetylenic-GABA on the resting and stimulated release of GABA in vivo.
Brain Res. 1980 Jun 9;191(2):471-81. doi: 10.1016/0006-8993(80)91295-0.
3
Biochemical correlates of GABA function in rat cortical neurons in culture.
Brain Res. 1980 May 19;190(1):123-38. doi: 10.1016/0006-8993(80)91164-6.
4
Physiological identification of GABA as the inhibitory transmitter for mammalian cortical neurons in cell culture.
Brain Res. 1980 May 19;190(1):111-21. doi: 10.1016/0006-8993(80)91163-4.
5
Effects of gamma-acetylenic GABA and gamma-vinyl GABA on synaptosomal release and uptake of GABA.
Biochem Pharmacol. 1981 Jun 1;30(11):1203-9. doi: 10.1016/0006-2952(81)90298-7.
6
Measurement of release of endogenous GABA and catabolites of [3H]GABA from synaptosomal preparations using ion-exchange chromatography.
Neurochem Res. 1982 May;7(5):589-99. doi: 10.1007/BF00965125.
7
Anticonvulsant action in mice with sound-induced seizures of the optical isomers of gamma-vinyl GABA.
Eur J Pharmacol. 1983 Apr 22;89(1-2):149-52. doi: 10.1016/0014-2999(83)90620-9.
8
Characterization of uptake and release processes for D- and L-aspartate in primary cultures of astrocytes and cerebellar granule cells.
Neurochem Res. 1983 Feb;8(2):231-43. doi: 10.1007/BF00963923.
9
Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy.
Acta Neurol Scand. 1983 Jul;68(1):34-9. doi: 10.1111/j.1600-0404.1983.tb04812.x.
10
Biochemical and clinical effects of gamma-vinyl GABA in patients with epilepsy.
Neurology. 1984 Feb;34(2):182-6. doi: 10.1212/wnl.34.2.182.
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