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L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor

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Abstract

Our earlier observations showed thatl-lysine enhanced the activity of diazepam against seizures induced by pentylenetetrazol (PTZ), and increased the affinity of benzodiazepine receptor binding in a manner additive to that caused by γ-aminobutyric acid (GABA). The present paper provides additional evidence to show thatl-lysine has central nervous system depressant-like characteristics.l-lysine enhanced [3H]flunitrazepam (FTZ) binding in brain membranes was dose-dependent and stimulated by chloride, bromide and iodide, but not fluoride. Enhancement of [3H]FTZ binding byl-lysine at a fixed concentration was increased by GABA but inhibited by pentobarbital between 10−7 to 10−3M. While GABA enhancement of [3H]FTZ binding was inhibited by the GABA mimetics imidazole acetic acid and tetrahydroisoxazol pyridinol, the enhancement by pentobarbital andl-lysine of [3H]FTZ binding was dose-dependently increased by these two GABA mimetics. The above results suggest thatl-lysine and pentobarbital acted at the same site of the GABA/benzodiazepine receptor complex which was different from the GABA binding site. The benzodiazepine receptor antagonist imidazodiazepine Ro15-1788 blocked the antiseizure activity of diazepam against PTZ. Similar to pentobarbital, the anti-PTZ effect ofl-lysine was not blocked by Ro15-1788. Picrotoxinin and the GABA, receptor antagonist bicuculline partially inhibitedl-lysine's enhancement of [3H]FTZ binding with the IC50s of 2 μM and 0.1 μM, respectively. The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding byl-lysine. This article shows the basic amino acidl-lysine to have a central nervous system depressant characteristics with an anti-PTZ seizure activity and an enhancement of [3H]FTZ binding similar to that of barbiturates but different from GABA.

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Author notes

  1. Xue-Min Gao

    Present address: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, 21228, Baltimore, Maryland

Authors and Affiliations

  1. Department of Biochemistry, University of Maryland Dental School, 666 West Baltimore Street, 21201, Baltimore, MD, USA

    Yung-Feng Chang & Xue-Min Gao

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  1. Yung-Feng Chang
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Chang, YF., Gao, XM. L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor. Neurochem Res 20, 931–937 (1995). https://doi.org/10.1007/BF00970739

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