Benzodiazepine Receptors and Their Relationship to the Treatment of Epilepsy

@article{Meldrum1986BenzodiazepineRA,
  title={Benzodiazepine Receptors and Their Relationship to the Treatment of Epilepsy},
  author={Brian S. Meldrum and Astrid G. Chapman},
  journal={Epilepsia},
  year={1986},
  volume={27}
}
Summary: Benzodiazepines (BDZ) interact with components of neuronal membranes to modify excitability in three different ways. (1) Action at a high affinity central receptor (dissociation constant, KD, of 3 nM) linked to the GABAA recognition site enhances the inhibitory action of GABA by increasing the number of openings of Cl‐ channels produced by a given concentration of GABA. This effect correlates with anticonvulsant activity as evaluated in the antipentylenetetrazol test in animals and… 
Peripheral benzodiazepine receptors in platelets of epileptic patients.
TLDR
PBZR receptor density was increased in platelets of patients taking a polypharmacy regime including the benzodiazepine clobazam and also in those receiving sodium valproate as monotherapy, but the significance is unclear.
Clinical Pharmacology and Mechanism of Action of Zonisamide
  • V. Biton
  • Biology, Psychology
    Clinical neuropharmacology
  • 2007
TLDR
It seems that the multiple pharmacological actions of zonisamide may contribute to the seizure reductions observed in a wide range of epilepsies and may help to preserve efficacy in individual patients despite possible changes in electrophysiological status.
MANAGEMENT OF CONVULSIONS IN NERVE AGENT ACUTE POISONING: A POLISH PERSPECTIVE
TLDR
Imidazenil, an imidazobenzodiazepine derivative, may become the drug of choice in the management of convulsions in acute OP poisonings, and its effects on anticonvulsant activity are presented and discussed.
GABAergic mechanisms in the pathogenesis and treatment of epilepsy.
  • B. Meldrum
  • Psychology, Biology
    British journal of clinical pharmacology
  • 1989
TLDR
Experimental data suggest that the best prospect for potent anticonvulsant action with fewest side effects (myoclonus, sedation, ataxia) is at present offered by GABA-transaminase inhibitors or novel agents acting on the benzodiazepine receptor site.
Classification of GABA and benzodiazepine receptors
  • B. Meldrum
  • Biology
    Journal of psychopharmacology
  • 1987
GABA (4-aminobutyric acid) is the principal inhibitory neurotransmitter in the brain acting both postsynaptically on dendrites, the somatic membrane and the axon initial segment, and presynaptically
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 81 REFERENCES
GABA‐Benzodiazepine‐Barbiturate Receptor Interactions
  • R. Olsen
  • Biology
    Journal of neurochemistry
  • 1981
TLDR
Evidence supports the model for a complex containing receptor sites for GABA, benzodiazepines, and picrotoxininl barbiturates, as well as the chloride ionophore, and thus the relevance of GABA to the actions of the other drugs.
Ethyl β-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats
TLDR
It is reported here that, in contrast to the benzodiazepines, β-CCE lowers seizure threshold and reverses the sedative effect of flurazepam, and if β- CCE has a close structural relationship to the endogenous ligand, benzodiazines may be antagonistic at the receptor site.
GABA reduces binding of 3H-methyl β-carboline-3-carboxylate to brain benzodiazepine receptors
TLDR
Binding of the methyl ester of β-carboline-3-carboxylic acid (β-CCM), which by itself is a convulsant, is investigated and it is reported that 3H-β- CCM binds to brain benzodiazepine receptors and that, in contrast to binding of3H-diazepam, 2H- β-CCC binding is reduced by GABA in a bicuculline-sensitive manner.
In vivo receptor occupation by benzodiazepines and correlation with the pharmacological effect
A study on benzodiazepine receptor binding in audiogenic seizure-susceptible rats.
TLDR
The findings indicate that a disturbance at the level of the benzodiazepine receptor/GABA receptor/chloride channel complex is not a likely general aetiological factor for audigenic seizures in rats.
Inhibition of Ca2+ conductance in identified leech neurons by benzodiazepines.
TLDR
Findings indicate that BZs act like Ca2+-channel antagonists in intact neuronal preparations and are consistent with the hypothesis that Bz binding to micromolar-affinity receptors modulates voltage-gated Ca2-channel channels.
Interaction of convulsive ligands with benzodiazepine receptors.
TLDR
During structural modification of ethyl beta-carboline-3-carboxylate an agent was discovered which has high affinity for brain benzodiazepine receptors but which is a potent convulsant, which may explain the convulsive properties.
...
1
2
3
4
5
...