Introduction: CLOBAZAM is an anticonvulsant drug. Its side effects on reproductive functions have not been sufficiently studied. This study was designed to evaluate the effect of CLOBAZAM on pituitary-gonad axis and spermatogenesis in adult male rats.Materials and Methods: 40 adult male rats wistar strain were randomly divided into five groups. Animals in group1 (Control group) were injected with any treatment. Animals in group2 (Sham group) received the three-component solvent (propylenglycol, ethanol and distilled water in a ratio of 5: 2: 3) in a corresponding volume, i.e.1ml/kg.bw.Animals in groups 3, 4, and 5 received CLOBAZAM (dissolved in solvent), respectively, in doses of 2.5, 5, and 10 mg/kg.bw/day i.p. for 21 days. At the end of the study, blood gonadotropins (LH and FSH) levels as well as testosterone of rats in five groups were determined. The animals were sacrificed, then, spermatogram and histological changes of their testes were studied under light microscope.Results: The results show that in CLOBAZAM treated groups, particular experimental group 3, blood testosterone levels were significantly decreased as compared to the control group. Plasma concentrations of LH, FSH assayed and there were no significant differences among the CLOBAZAM treated groups as compared with control group. Body weight in CLOBAZAM treated relatively increased. However, sperm density and testes weight were not different from those of the control group.Conclusion: These findings indicate that CLOBAZAM has a relative suppressive influence on reproductive function in rats. We suggest that CLOBAZAM directly affects production of testosterone in leydig cells or centrally increased estradiol biosynthesis subsequently lowered testosterone levels by negative feedback.

Background and purpose: Febrile seizure is a seizure associated with fever without any evidence of intracranial infection or electrolytic disorder. Its treatment includes anticonvulsant medicines administered for preventing recurrence. In this research, treatments with diazepam and CLOBAZAM were evaluated in preventing febrile seizure recurrence among patients admitted to Taleghani Hospital.Material and Methods: The study population included 150 patients with simple febrile seizure aged between six months to six years of old. They were randomly assigned into two groups to receive either diazepam or CLOBAZAM after control of seizure. The patients received diazepam 0.33 mg/kg/ dose every 8h and CLOBAZAM in 2.5, 5, 7.5, and 10 mg/kg every 12 h. The results involving fever episodes in each 3 months, side effects of medicines and recurrence were recorded in a check list and then analyzed.Results: Among the patients 32 were excluded and 118 patients including 61 in diazepam group and 57 in CLOBAZAM group were studied. There were 62 males and 56 females in this population. The mean age was 21.05±10.10 months and 21.96±10.74 months in diazepam and CLOBAZAM groups, respectively and 21.49±10.39 in total population. There was no significant difference between the two groups in recurrence of febrile seizure (P>0.05). No significant difference was found in incidence of ataxia between the two groups. In the group receiving diazepam 45.9% of the patients had drowsiness compared to 8.8% in clobazm group (P>0.05). No significant difference was found between the studied groups for medicinal side effects including ataxia, vomiting, anorexia, and irritability (P>0.05).Conclusion: Treatment by CLOBAZAM caused recurrence and complications less than diazepam. However, more studies including larger sample sizes are required to confirm these results.

BACKGROUND: Epilepsy is one of the major neuron-damaging neurological disorders. Generalized tonic-clonic seizure (GTCS) is the commonest one. Refractory patterns cannot be controlled by simple monotherapy with antiepileptic drugs (AEDs). Valproic acid (VPA) is one of the widely prescribed AEDs but it may not control many cases up to its maximum tolerable doses. In this study, we have seen the safety and efficacy of CLOBAZAM to control seizure in the adult population as an add-on drug over valproate, in cases of valproate uncontrolled seizures. MATERIALS AND METHODS: Patients on VPA monotherapy but not responding to it were recruited after applying inclusion and exclusion criteria and CLOBAZAM was added. There were two follow-ups at the interval of 6 months each. Seizure frequency and quality of life inventory in epilepsy-31 items (QOLIE-31) score were recorded to denote efficacy, and the occurrence of any adverse effect was also noted to elicit safety. RESULTS: Out of 101 patients, 78 were male and 23 were female. The most common age group was 18–30 y. Seizure frequency from 2. 99 ± 0. 95 decreased significantly on the third visit to 0. 25 ± 0. 43. QOLIE-31 scores of seizure worry, overall quality, emotional well-being, and cognition improved in the second follow-up. Fatigue, somnolence, and weight gain were the major side effects. CONCLUSION: CLOBAZAM could be a good choice as an add-on in GTCS not controlled with VPA monotherapy. CLOBAZAM definitely reduces seizure frequency and seizure worry and improves cognitive function and overall quality of life.

The solvatochromic behaviour of two ketonic derivatives of benzodiazepine namely 7-chloro-1-methyl-5-phenyl-1, 5-benzodiazepine-2, 4-dione (CLOBAZAM® ) and 5, (2-chlorophenyl)-7-nitro-2, 3-dihydro-1, 4-benzodiazepine-2-one (Clonazepam® ) were analysed in some selected solvents of different polarities using UV-Visible spectroscopy and DFT computational techniques. The solute-solvent interactions were evaluated by means of Kamlet-Taft’ s Linear Solvation Energy Relationship (LSER) concept. The results show that electronic absorption properties of the compounds depend on the solvent polarity and both specific and non-specific interactions between solute and solvent. Also, the spectral properties show satisfactory correlation with solvatochromic parameters (α , β and π ). The plot of ῡ max calculated against ῡ max observed in the representative solvents gives a good linear regression value of R2=0. 998. The results of Frontier Orbital calculations showing the differences between HOMO and LUMO of the ground states and various excited states of CLOBAZAM® and Clonazepam® are-5. 15eV and-4. 20eV respectively and both are in good agreement with the most important transitions observed in the two compounds.

Background: Epilepsy is the second common neurologic disorder. Although many antiepileptic drugs have been formulated to control the seizures, but not all seizures have been controlled by them Uncontrolled epilepsy can actually reduce the patients’ quality of life.Objectives: Identifying the proportion of adult intractable epilepsy among epileptic patients in an area in the North East of Iran.Materials and Methods: All epileptic patients who admitted to neurology clinic of a teaching hospital associated with Islamic Azad University of Mashhad in 2014 that were eligible for inclusion criteria enrolled this cross-sectional study. After fulfilling the informed consent, interview, examination and EEG were done. The data was expressed and analyzed by using Mean±Standard deviation and the Likelihood Ratio Chi-Square test in SPSS software version 22. Significance level was considered as less than 0.05%.Results: From 171 patients, 59 patients with epilepsy (34.5%) met the criteria for intractable epilepsy (37.5% male, 31.3% female) with mean age of 28.2±8.5 years. The mean duration of disease was 14.5±8.4 and 11±8.8 years in patients with refractory epilepsy and controlled epilepsy respectively (t-test=2.5 and p=0.013). The seizure frequency was significantly higher in pharmacoresistant patients than pharmacoresponsive ones (7.15±8.4 vs. 0.29±7 per month p=0.0001). Also taking Carbamazepin and CLOBAZAM and Primidone were associated with intractable epilepsy (p<0.05).Conclusions: Our results accounted that about one-third of patients with epilepsy are categorized in refractory epilepsy with higher duration of disease.

Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are among the most severe dermatologic reactions to the drugs. Data about SJS and TEN among pediatric population especially in Iran is limited. This study aimed to investigate the clinical and para-clinical characteristics of pediatric patients with SJS/TEN. Materials and Methods From 2010 to 2016, all SJS and TEN children from three teaching hospitals in Mashhad-Iran with age less than 15 years were included in the study. Patients’ catechistic, history, physical examinations, progress notes, laboratory findings, medical consults, treatments taken and the final outcome were extracted from medical records by researcher. Data were further analyzed by SPSS (version 17. 0). Results Among 165 records, 48 children (58. 3% male; mean age of 9. 1 years) were among the SJS and TEN spectrum. Anticonvulsants (50%; including lamotrigine, phenobarbital, phenytoin, carbamazepine, valproate and CLOBAZAM) were the most common drugs followed by antibiotics (38. 1%; including cefixime, penicillin, azithromycin, co-amoxiclav, cephalexin, co-trimoxazole and ceftriaxone), and analgesics (9. 5%; including acetaminophen, ibuprofen and naproxen). Infectious agents were the possible cause of SJS/TEN in two patients. WBC counts, liver function tests, renal and electrolyte tests were significantly different in SJS and TEN groups. Conclusion The main suspected medications found in this study were anticonvulsants and antibiotics and the mortality rate was 12. 5%. The main suspected medications found in this study were anticonvulsants and antibiotics and the mortality rate was 12. 5%.

Activation of chloride gated GABA receptors regulates the excitatory transmission in the epileptic brain. Positive allosteric modulation of these receptors via distinct recognition sites is the therapeutic mechanism of antiepileptic agents which prevents the hyperexcitability associated with epilepsy. These distinct sites are based on subunit composition which determines binding of various drugs like benzodiazepines. The binding of antiepileptic agents to this recognition site increases the affinity of GABA receptor for modulating the inhibitory effects of GABA-induced chloride ion flux. In the pentameric complex structure of these receptors, the a/g interface forms the benzodiazepine (BZD) binding site on extracellular domain. Thus the a subunit is shown as highly required for functional modulation of the receptor channels by benzodiazepines. The extracellular domain of a subunit of human GABAA is modeled and docking studies are performed with clonazepam, CLOBAZAM, clorazepate, diazepam, midazolam, lorazepam. In order to accomplish this, the amino acid sequences human gamma-aminobutyric acid receptor subunit alpha-1 precursor was obtained from National Center for Biotechnology Information. Three-dimensional structure of protein sequences were received from phyre2 protein fold recognition server. Molecular and structural properties of drugs were taken by drug bank server. Autodock4.2 software was used for docking purpose. This study shows hydrogen bond interactions of GABRA1 with selected drugs and binding modes and the interacting amino acid residues involved in recognition of the compound. The results obtained from this study would be useful in understanding the modulatory mode of GABRA1 with benodiazipine drugs.