Effects of Clobazam and Its Active Metabolite on GABA‐Activated Currents in Rat Cerebral Neurons in Culture

  title={Effects of Clobazam and Its Active Metabolite on GABA‐Activated Currents in Rat Cerebral Neurons in Culture},
  author={Fumihiro Nakamura and S. Suzuki and Shigeko Nishimura and Kazuichi Yagi and M Seino},
Summary: Purpose: The antiepileptic effects of clobazam, a 1,5‐benzodiazepine, have been well documented in animal experiments and clinical trials. However, the drug's mechanisms of antiepileptic actions are still undetermined. The purpose of this study was to learn how clobazam and its active metabolite modulate γ‐aminobutyric acid (GABA)‐activated currents in rat cerebral neurons in culture. 

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABAA‐Receptor Channels

Stiripentol is currently an efficient drug for add‐on therapy in infantile epilepsies because it improves the efficacy of antiepileptic drugs (AEDs) through its potent inhibition of liver cytochromes P450.

Antihyperalgesic Effect of the GABAA Ligand Clobazam in a Neuropathic Pain Model in Mice: A Pharmacokinetic–Pharmacodynamic Study

Clobazam showed a dose‐dependent antihyperalgesic effect in the chronic constriction injury model of neuropathic pain, peaking at 1 hr after administration and lasting for 4 hr with no relevant sedation at a dose of 3 mg/kg.

GABAA Receptor Physiology and Its Relationship to the Mechanism of Action of the 1,5-Benzodiazepine Clobazam

Clobazam was synthesized with the anticipation that its distinct chemical structure would provide greater efficacy with fewer benzodiazepine-associated adverse effects, and evidence gathered from approximately 50 epilepsy clinical trials indicated that the sedative effects observed with clobzam treatment were less severe than those reported with 1,4-benzodiazepines.

Modulation of native GABAA receptor activity by triazolo 1,5-benzodiazepines

Interactions between modulators of the GABA(A) receptor: Stiripentol and benzodiazepines.

  • J. Fisher
  • Biology, Medicine
    European journal of pharmacology
  • 2011

GABAA Receptors of Cerebellar Granule Cells in Culture: Interaction with Benzodiazepines

It is shown how rat cerebellar granule cells in culture may be a useful model for studying new benzodiazepine site agonists based on the pharmacological separation of diazepam-sensitive α1 β2/3 γ2 receptors from those which are diazepAM-insensitive and contain the α6 subunit.

Clobazam as an adjunctive therapy in treating seizures associated with Lennox–Gastaut syndrome

Clinical trials involving clobazam as an addon therapy in a variety of pediatric epilepsy populations have found a significant improvement in seizure control, and longstanding clinical experience suggests that clobrazam is a safe and well tolerated antiepileptic drug with infrequent and mild adverse effects.



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The metabolite formed after clobazam administration accounted for the persistence of antileptazol activity in this animal species.

Plasma concentrations of clobazam and its N‐desmethyl metabolite; protection against pentetrazol‐induced convulsions in mice

The anticonvulsant effects of acute administration of clobazam and its principal metabolite N‐desmethyl‐clobazam were studied in mice. Pentetrazol, given by slow intravenous infusion 1 or 2 h after

Species differences in clobazam metabolism and antileptazol effect

The antileptazol effect of clobazam lasts longer in the mouse than in the rat, and the longer duration in mice than in rats seems to be associated with different brain accumulations of the metabolite.

Pharmacology of anti-anxiety drugs with special reference to clobazam.

The advantage of clobazam compared with the 1.4 benzodiazepines lies mainly in the fact that motor activity is influenced only after very high doses, these doses being markedly above those required to induce tranquillizing and anti-agression activities.

Antiepileptic Properties of Clobazam, a 1–5 Benzodiazepine, in Man

There is an urgent need for intensive study of the basic mechanism governing exhaustion of the antiepileptic properties of the benzodiazepines in general and of clobazam in particular.

Effects of benzodiazepines and non‐benzodiazepine compounds on the GABA‐induced response in frog isolated sensory neurones

The experimental system of frog isolated sensory neurones and a ‘concentration‐clamp’ technique appears to be useful for evaluating efficacy of compounds on responses mediated by the GABA/benzodiazepine receptor‐chloride channel complex.

Add-on trial of clobazam in intractable adult epilepsy with plasma level correlations.

Clobazam appears to be a safe and effective add-on antiepileptic for a wide variety of seizure types in intractable epilepsy.

Comparative Study in Mice of Ten 1,4‐Benzodiazepines and of Clobazam: Anticonvulsant, Anxiolytic, Sedative, and Myorelaxant Effects

Despite the caution needed in the extrapolation of the results from animals to humans, this work stresses the interesting place that the 1,5‐benzodiazepine seem to hold as anticonvulsant in clinical practice.