Correlation between enhancement of [3H]flunitrazepam binding and suppression of pentylenetetrazol-induced seizures by L-lysine.

  title={Correlation between enhancement of [3H]flunitrazepam binding and suppression of pentylenetetrazol-induced seizures by L-lysine.},
  author={Y. F. Chang and X. -M. Gao and Jay S. Chen},
  journal={European journal of pharmacology},
  volume={193 2},
L-Lysine enhanced the specific [3H]flunitrazepam (FTZ) binding of bovine brain membranes in vitro. Inhibition of specific [3H]FTZ binding to brain membranes in vitro by pentylenetetrazol (PTZ) at concentrations 0.46 mM and below was reversed by increasing L-lysine concentrations in the incubation mixture; further increase of L-lysine concentration enhanced this binding. However, inhibition of [3H]FTZ binding by PTZ higher than 2.3 mM was reversed only partially by L-lysine. L-Lysine enhanced… 
L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor
The basic amino acidl-lysine is shown 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.
Chronic L-lysine develops anti-pentylenetetrazol tolerance and reduces synaptic GABAergic sensitivity.
After 15- and 20-day treatment, clonic and tonic seizures latencies and survival rate decreased, suggesting development of tolerance, and L-lysine enhanced the specific [35S]tert-butyl bicyclophosphorothionate binding in brain membranes dose dependently.
Chronic pretreatment with naloxone modifies benzodiazepine receptor binding in amygdaloid kindled rats
It is indicated that previous chronic exposure to naloxone increases BDZ receptor binding in kindled rats, and suggests that this effect may be associated with the enhanced seizure suppression observed in these animals.
Anticonvulsant and depressant effects of aqueous extracts of Carum copticum seeds in male rats
The results indicate that aqueous extracts of CCS have a significant anticonvulsant effect and significantly delayed the incidence of every seizure stage in the PTZ model of kindling.
GABA and opioid binding distribution in the brain of the seizure‐resistant Proechimys guyannensis: An autoradiography study
Findings provide the first description of receptor binding distribution of the Proechimys brain and suggest natural endogenous anticonvulsant mechanisms of theses rodents under normal conditions.
Effects of chronic morphine pretreatment on amygdaloid kindling development, postictal seizure and suppression and benzodiazepine receptor binding in rats
It is indicated that the previous experience with chronic morphine modifies the kindling process and that the enhanced BDZ receptor binding detected in the authors' experiments may be involved in the enhanced postictal seizure suppression observed in these animals.
Chapter 9 GABAA Receptor-Activated Chloride Channels
Publisher Summary About 30% of neurons in the brain, particularly small interneurons, are thought to be gamma-aminobutyric acid (GABA)ergic (contain GAD) and most neurons responds to γ-Aminobutyric
Role of endothelial nitric oxide generation and peroxynitrite formation in reperfusion injury after focal cerebral ischemia.
The hypothesis that in addition to the detrimental action of NO formed by neuronal NOS during ischemia, NO generation at reperfusion plays a significant role in reperfusions injury, possibly through peroxynitrite formation is supported.
ИММУНОТРОПНЫЕ ЭФФЕКТЫ L-АРГИНИНА В ИСХОДНОМ СОСТОЯНИИ И В УСЛОВИЯХ ЭМОЦИОНАЛЬНО-БОЛЕВОГО СТРЕССА © Северьянова Л.А., Бобынцев И.И., Крюков А.А., Долгинцев М.Е. Кафедра патофизиологии Курского государственного медицинского университета
Исследовано влияние малых доз L-аргинина (от 15 до 450 мкг/кг) на эффекторные звенья гуморального и клеточного иммунного ответа у крыс и активность нейтрофилов у мышей в исходном состоянии и в


Enhancement of benzodiazepine receptor binding by L-lysine is chloride-dependent and due to increase in binding affinity.
L-Lysine enhanced specific [3H]flunitrazepam binding dose dependently on extensively washed bovine brain membrane in vitro and may act on a distinct picrotoxinin-sensitive site which was distinct from the gamma-aminobutyric acid receptor site.
[35S]-t-butylbicyclophosphorothionate binding sites are constituents of the gamma-aminobutyric acid benzodiazepine receptor complex
  • P. Supavilai, M. Karobath
  • Chemistry, Medicine
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1984
Using conventionally prepared washed membrane fractions from rat cerebral cortex, it is confirmed that in the presence of 200 mM NaBr [35S] TBPS binds to a high affinity population of binding sites and that muscimol inhibits [ 35S]TBPS binding (IC50 0.32 microM) allosterically.
Studies on the relationship of gamma-aminobutyric acid-stimulated diazepam binding and the gamma-aminobutyric acid receptor.
The observed relationship between [3 H]-muscimol-binding sites and the degree of GABA-stimulated [ 3 H]diazepam binding suggests that the high affinity musciml-binding site is not mediating the GABA enhancement effect.
Effects of tetrazole derivatives on [3H]diazepam binding in vitro: correlation with convulsant potency.
Results suggest that pentamethylenetetrazole and related tetrazole derivatives may elicit their convulsant effects by interaction with the benzodiazepine receptor.
Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain.
A very good correlation was observed between their relative affinities for the [35S]-TBPS binding site and their convulsant potencies, indicating that pentamethylenetetrazol and related tetrazoles may produce their Convulsant and anxiogenic actions via the GABA-benzodiazepine-chloride ionophore receptor complex.
Benzodiazepine receptors: labeling in intact animals with [3H] flunitrazepam.
In pharmacologically active doses sodium pentobarbital, strychnine, picrotoxin and bicuculline fail to influence [3H] flunitrazepam binding in vivo, and benzodiazepine potencies correspond to pharmacological potencies and parallel relative affinites for binding sites in isolated brain membranes.
Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures.
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).
Effects of l-lysine and its metabolites on pentylenetetrazol-induced seizures
The anticonvulsant activity of lysine and its metabolites was explained on the basis of their connection with the GABAergic transmission.
Anticonvulsant properties of some benzodiazepines.
In view of the favorable profile of anticonvulsant action of compound 1 and the unique antipentylenetetrazol activity of compound 5, these, and possibly other henzodiazepines included in this study, appear worthy of cautious clinical trial in epilepsy.
Interactions of pentamethylenetetrazole and tetrazole analogues with the picrotoxinin site of the benzodiazepine-GABA receptor-ionophore complex.
The results suggest that tetrazoles may produce convulsions by acting at the picrotoxin-sensitive site of the benzodiazepine-GABA receptor-ionophore complex.