Neurochemical Research

, Volume 20, Issue 8, pp 931–937 | Cite as

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

  • Yung-Feng Chang
  • Xue-Min Gao
Original Articles


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.

Key Words

Amino acids barbiturates GABA-benzodiazepine receptor complex neuromodulator receptor binding convulsions 


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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Yung-Feng Chang
    • 1
  • Xue-Min Gao
    • 1
  1. 1.Department of BiochemistryUniversity of Maryland Dental SchoolBaltimoreUSA

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