Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90207-X· OSTI ID:6281816

Chang, Y F; Hargest, V; Chen, J S

L-lysine and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine of L-Pa i.p. significantly increased clonic and tonic latencies in a dose-dependent manner against 90 mg/kg PTZ-induced seizures. L-Lysine but not L-Pa enhanced the anticonvulsant effect of diazepam (DZ). L-Pa i.c.v. showed a slight decrease in clonic latency; it did not enhance the antiseizure activity of DZ; it caused seizures at 0.6 mmol/kg. D-PA i.c.v. displayed an opposite effect compared to its L-isomer. The anticonvulsant effect of L-lysine in terms of increase in seizure latency and survival was even more amplified when tested with a submaximal PTZ concentration. L-Lysine showed an enhancement of specific /sup 3/H-flunitrazepam(FZ) binding to mouse brain membranes both in vitro an din vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of /sup 3/H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor.

• Research Organization: Univ. of Maryland, Baltimore (USA)
• OSTI ID: 6281816
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 43:15; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
ANTICONVULSANTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRAIN
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
IN VITRO
IN VIVO
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYSINE
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
METABOLITES
MICE
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RECEPTORS
RODENTS
SURVIVAL TIME
TRACER TECHNIQUES
TRANQUILIZERS
TRITIUM COMPOUNDS
VERTEBRATES