Disease relevance of Clorepin

• Phenytoin toxicity due to interaction with clobazam [1].
• After 3 weeks of treatment with clobazam 20 mg a day, the patient developed, in association with his seizures, a neologistic jargon dysphasia but with loss of inflection, volume, and rhythm of speech, presumably as a result of the effect of the clobazam [2].
• Use of clobazam in certain forms of status epilepticus and in startle-induced epileptic seizures [3].
• However, tolerance to the protection from the full tonic clonic seizure in DBA/2 mice could not be detected, even when the dose of clobazam was reduced to the smallest dose that acutely protected most of the mice [4].
• Carbamazepine intoxication with negative myoclonus after the addition of clobazam [5].

Psychiatry related information on Clorepin

• Results of studies of vigilance and psychomotor performance during therapeutic use in patients are less conclusive, but clobazam may be useful in anxious patients who experience such impairment with other benzodiazepines [6].
• Although subjective drowsiness has occurred with similar frequency with clobazam and diazepam in some studies, clobazam causes less objectively measured sedation or psychomotor impairment in experimental studies [6].
• On all five performance assessments (choice reaction times, serial subtraction times, critical flicker fusion values), there was a consistent tendancy for clobazam performance to be comparatively better under high stress, and for placebo performance to be comparatively better under low stress [7].
• Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine) [8].
• 3 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 [9].

High impact information on Clorepin

• BACKGROUND: Stiripentol is an inhibitor of cytochrome P450 that showed antiepileptic efficacy in severe myoclonic epilepsy in infancy (SMEI) in association with clobazam and valproate in an open study [10].
• A double-blind comparison of buspirone, clobazam, and placebo in patients with anxiety treated in a general practice setting [11].
• The single-dose pharmacokinetic profile of clobazam is highly predictive of drug behaviour during repeated dosage, suggesting that clobazam kinetics are dose- and concentration-independent within the range studied, and that self-induction or inhibition of clearance is not evident during 3 weeks of dosage [12].
• RESULTS: The mean (+/-standard deviation) urine 15-F(2t)-IsoP levels (nmol/mmol Cr) were: valproic acid (0.36 +/- 0.15); carbamazepine (0.24 +/- 0.10); clobazam (0.23 +/- 0.10); control group (0.20 +/- 0.09) [13].
• PURPOSE: To confirm the efficacy and to clarify the problems of clobazam (CLB) as a new antiepileptic drug (AED) and clorazepate (CLP) as an alternative AED in Japan. METHODS: CLB and CLP were added on or replaced with conventional AEDs in 55 and 170 patients with refractory epilepsies, respectively [14].

Chemical compound and disease context of Clorepin

• 1 In an uncontrolled clinical trial, carried out in 11 psychiatric patients with the clinical diagnoses of anxiety neurosis and depressive neurosis, clobazam, a new benzodiazepine preparation, in the dosage range 10-60 mg daily produced statistically significant improvement in the total and both factor scores of the Hamilton Anxiety Scale (HAM-A) [15].
• 1 Laboratory tests of psychomotor performance and 'on road' assessments of car handling ability were made following repeated doses of clobazam 10 mg three times daily, lorazepam 1 mg three times daily and matching placebo 1 capsule three times daily [16].
• 3. These results indicate improved reaction time and memory performance with repeated dosing of clobazam in contrast to buspirone [17].
• 1 Three studies are described, the first being a comparison of the effects of acute night-time doses of clobazam 20 mg, amylobarbitone sodium 100 mg, nitrazepam 5 mg and placebo, on choice reaction time, critical flicker fusion (CFF) and stabilometer performance [18].
• 2 No effect of clobazam or triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep [19].

Biological context of Clorepin

• Clobazam was administered in 13 patients; 15.4% of them were completely unresponsive, 23.1% experienced drug resistance, and 61.5% obtained a good control (91.5% reduction of the reflex seizures) for a mean of 22.75 months [20].
• Clobazam, 20 or 30 mg/day was given for 10 days around menstruation in successive menstrual cycles to 13 women who had responded favourably to this drug in an earlier short-term placebo controlled cross-over study [21].
• The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam [22].
• The pharmacokinetics of clobazam were studied in six healthy volunteers and six age and sex matched enzyme-induced epileptic patients [23].
• The increase in AUC for NDMC generated from clobazam was also relatively greater than that for NDMC administered orally [24].

Anatomical context of Clorepin

• The experiment was repeated using a different protocol with minimized environmental stimuli and no amygdala stimulation during chronic clobazam administration [25].
• These audiogenic-like seizures were blocked by clobazam microinjection into the substantia nigra (SN) and partially modified by SN vehicle injection [26].
• Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. II. Effects of nigral clobazam microinjections [26].
• In guinea-pig hippocampal synaptosomes, minaprine (50 nM) also reduced the TFMPP-induced inhibition of 3H-ACh release, whilst clobazam (50 nM) was inactive [27].
• However, the K(i)'s for diazepam and for clobazam to displace [(3)H]RY-80 binding in hippocampus were about fourfold higher than for [(3)H]flunitrazepam, and the K(i) for clonazepam was sixfold larger, suggesting that these benzodiazepine receptor agonists bind with relatively lower affinity at hippocampal alpha 5-containing receptors [28].

Associations of Clorepin with other chemical compounds

• Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses [29].
• SE remission was obtained with the usual antiepileptic drug therapy (diazepam, clobazam, valproate) [30].
• 1. The single dose pharmacokinetics of N-desmethylclobazam (NDMC) and clobazam were studied in eight healthy male volunteers [31].
• 2 Clobazam, a novel 1,5 benzodiazepine, and diazepam were compared with placebo in a double-blind group comparative trial in general practice, which was designed to avoid as many confounding variables as possible [32].
• Simple and sensitive method for the determination of clobazam, clonazepam and nitrazepam in human serum by high-performance liquid chromatography [33].

Gene context of Clorepin

• CYP3A4 and CYP2C19 are the main P450s involved in clobazam metabolism [34].
• Clobazam for epilepsy [35].
• Anticonvulsant action of a 1,5-benzodiazepine, clobazam, in reflex epilepsy [36].
• In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19 [34].
• Forensic intoxication with clobazam: HPLC/DAD/MSD analysis [37].

Analytical, diagnostic and therapeutic context of Clorepin

• The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of standard antiepileptic drug therapy [38].
• This suggestion was supported by their clinico-EEG findings, including the effect of a single oral dose of clobazam (CLB) on EEG [39].
• Clobazam, an anxiolytic 1,5-benzodiazepine, has been evaluated as an anticonvulsant in 2 animal models [36].
• PURPOSE: The antiepileptic effects of clobazam, a 1,5-benzodiazepine, have been well documented in animal experiments and clinical trials [40].
• The analysis of clobazam and its metabolite desmethylclobazam by high-performance liquid chromatography [41].

References