Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures.
L-lysine, an essential amino acid for man and animals, and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine or 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) (0.2 mg/kg). L-PA (0.1 mmol/kg) 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 (0.1 mmol/kg) 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 (65 mg/kg). L-Lysine showed an enhancement of specific 3H-flunitrazepam (FZ) binding to mouse brain membranes both in vitro and in vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of 3H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor.
Chang
Y F
YF
Department of Biochemistry, University of Maryland Dental School, Baltimore 21201.
Hargest
V
V
Chen
J S
JS
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005445:Flunitrazepam / Q000378:metabolism; D008239:Lysine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D010875:Pipecolic Acids / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*
D010875:Pipecolic Acids; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C031345:pipecolic acid; D008239:Lysine; D003975:Diazepam; D010433:Pentylenetetrazole