L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor.
Our earlier observations showed that L-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 gamma-aminobutyric acid (GABA). The present paper provides additional evidence to show that L-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 by L-lysine at a fixed concentration was increased by GABA but inhibited by pentobarbital between 10(-7) to 10(-3)M. While GABA enhancement of [3H]FTZ binding was inhibited by the GABA mimetics imidazole acetic acid and tetrahydroisoxazol pyridinol, the enhancement by pentobarbital and L-lysine of [3H]FTZ binding was dose-dependently increased by these two GABA mimetics. The above results suggest that L-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 of L-lysine was not blocked by Ro15-1788. Picrotoxinin and the GABA, receptor antagonist bicuculline partially inhibited L-lysine's enhancement of [3H]FTZ binding with the IC50s of 2 microM and 0.1 microM, respectively. The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding by L-lysine. This article shows the basic amino acid L-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.
Chang
Y F
YF
Department of Biochemistry University of Maryland Dental School, Baltimore 21201, USA.
Gao
X M
XM
D000818:Animals; D000838:Anions; D000927:Anticonvulsants / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D002417:Cattle; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D008239:Lysine / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000838:Anions; D000927:Anticonvulsants; D001463:Barbiturates; D001640:Bicuculline; D002492:Central Nervous System Depressants; D003975:Diazepam; D008239:Lysine; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid