The association between HLA-B*15:02 and phenytoin-induced severe cutaneous adverse reactions: a meta-analysis

Aim: Phenytoin (PHT) is a common anticonvulsant agent known for inducing severe cutaneous adverse reactions (SCARs). HLA-B*15:02 as a risk factor of PHT-induced SCARs was reported in numerous studies with inconsistent results. This meta-analysis aimed to establish pooling evidence of this association. Materials & methods: Pooled odds ratios (ORs) with 95% CIs were estimated using a random-effects model. Results: A total of 11 studies on 1389 patients, were included for the analyses. There was a significant association between HLA-B*15:02 and PHT-induced SCAR (pooled OR = 2.29, 95% CI: 1.25–4.19, p = 0.008). Furthermore, there was a significant association regarding Stevens–Johnson syndrome/toxic epidermal necrolysis (OR = 3.63, 95% CI: 2.15–6.13, p < 0.001) but no association regarding drug reaction with eosinophilia and systemic symptom. Conclusion: The results supported the recommendations of HLA-B*15:02 screening before treatment with PHT.

Cyclodextrin complexes of the anticonvulsant agent valproic acid

Six cyclodextrin (CD) complexes of the antiepileptic drug valproic acid (VAL) were prepared by kneading and/or co-precipitation methods and characterized by thermal analysis, powder X-ray diffraction and spectroscopic (1H NMR...

Açaí: potential anticonvulsant agent

Background: Convulsion is an involuntary contraction of skeletal muscles. When considering vulnerable populations exposed to the mentioned pathophysiological situation, it is recognized that many of them will not have access to the indicated pharmacological treatment. Therefore, the ingestion of açai, Euterpe oleracea (EO) attenuates the problem, acting as an anticonvulsant. Objectives: evaluate the EO as an anticonvulsant agent. Design and setting: It is a bibliographic research and the data collection was done from the PubMed and Scielo databases. Methods: The descriptor used was “Euterpe oleracea” and the inclusion criteria adopted were: articles published in the last five years, available in full and publications related to epilepsy. Results: The EO acts on the GABAergic system when interacting occurs with the GABA receptor of cortical neurons and, above all, of astrocytes in an inhibitory mechanism for the uptake of the neurotransmitter GABA, that accumulates in the synaptic cleft, preventing the exaggerated neurotransmission that causes convulsions. In pentylenetetrazol-induced seizure (PTZ), EO showed some results similar to diazepam: reduced duration of tonic-clonic convulsion and increased latencies for the first myoclonic spasm and for the first generalized tonic-clonic seizure. Conclusions: Studies suggest that EO can be classified as an anticonvulsant, considering its inhibitory activity during synapses. Furthermore, the consumption of EO is more viable at a socioeconomic level compared to traditional drug treatments.

Recent Development in Substituted Benzothiazole as an Anticonvulsant Agent

: Heterocyclic compounds and its derivatives gained more attention due to their valuable biological and pharmacological properties. Benzothiazole is a heterocyclic structure containing bicyclic ring system with large panel of applications. The benzothiazole is present in many new products undergoing research with the hope that it possesses various biological activities. Epilepsy is a diverse group of diseases marked by neuronal excitability and hypersynchronous neuronal activity of motor, sensory or autonomic events with or without loss of consciousness.. Presently many antiepileptic drugs like Lamotrigine, stiripentol tiagabine, pregabalin, felbamate and topiramate are available and effective toward only 60-80% of patients along with undesirable side effects, such as hepatotoxicity, gastrointestinal disturbance, drowsiness, gingival hyperplasia, and hirsutism. Thus many attempts are still going on to develop antiepileptic drugs with safer profile. This review is mainly focus on compilation of reported scientific literature data in the recent one-decade on anticonvulsant activity of benzothiazole compounds.

2-Propyl-N′-[1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]pentanehydrazide

2-Propyl-N′-[1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]pentanehydrazide was obtained in 80% yield via the Einhorn variation of the Schotten–Baumann method by (+)-camphor hydrazide condensation with valproic acid (VPA) chloride. The structure of the titled compound was verified by Raman, FTIR, 1H-NMR, and 13C-NMR spectral analysis along with FAB-mass spectrometry. Thermal properties of synthesized derivative were elucidated by DSC and its purity by HPLC. The compound was successfully tested as a potential anticonvulsant agent based on models of chemically- and electrically-induced seizures.

Synthesis, in Vivo and in Silico Studies of N-Aryl-4-(1,3-Dioxoisoindolin-2-Yl)Benzamides as an Anticonvulsant Agent

Background: These days epilepsy is a common neurological disorder, which can affect on quality of life by unpredictable seizure. Thalidomide is one of the drugs to control the epilepsy but side effects such as teratogenicity, made it difficult to use. Methods: Six new analogues of N-aryl-4-(1,3-dioxoisoindolin-2-yl)benzamides were synthesized and tested for anti-seizure activity. To evaluate the anti-seizure activity of these new derivatives, 40 mice in 8 groups were received 10 mg/Kg of each new derivatives 30 min before the injection of pentylenetetrazole (PTZ, 70 mg/kg) to induced seizures. Latency time to first symptom of seizure was measured and compared to vehicle and standard groups. Docking methodology was applied to study on mode of interaction between GABAA receptor and synthetized compounds. Results: Structures of the all synthesized compounds were confirmed by NMR and mass spectroscopy. The latency time and mortality rate were individually measured for an hour after injection of pentylenetetrazole. Docking study revealed that synthesized compounds and thalidomide interact in similar conformation with GABAA receptor. Conclusion: The experimental and docking results were found in good correlation and demonstrated that the most active compound (5a), with 3,4-dimethylphenyl residue increased the duration of seizure inhibition threshold in comparison with thalidomide.

IN SILICO DESIGN OF POTENTIAL 1, 5-BENZOTHIAZEPINE DERIVATIVES AS AN ANTI - CONVULSANT AGENT BY MOLECULAR DOCKING STUDIES

Epilepsy is characterized by the presence of recurrent seizures. A seizure can be defined as “an episodic disturbance of movement, feeling, or consciousness caused by sudden synchronous, inappropriate, and excessive electrical discharges in the cerebral cortex”. One in every three patients with epilepsy is probable to be severely disabled. It is continuing this scenario as an attempt to develop potent and nontoxic anti-convulsant agents. Recently the discovery of benzothiazepine derivatives as an anticonvulsant agent is a significant area for research in medicinal chemistry as it is free from all side effects which is shown by a developed as an anticonvulsant agent. In this paper, we have presented results of 2D, and 3D docking poses studies of a series of 300 (Three series) molecules containing 1,5-benzothiazepine pharmacophore as anti-convulsant agents. Docking analysis was utilized to predict the mechanism of action of the designed derivatives for anticonvulsant potential. All the molecules exhibited a binding score in the range of -82.61 to - 118.25 kcal/mol. Most active molecules from Series 1, 2 and 3 exhibited hydrogen bond interactions with LEU282B, LEU282B and LEU282B. Also for the selected standard sodium phenytoin showed the hydrogen bond interaction with LYS637A. It was noted that the docking score of 1a to 10a, 101b to 110b and 201c to 210c was almost the same as that of selected standard sodium phenytoin. The protein showed hydrogen bonding with all synthesized compound showed potential against epilepsy with GABA nergic mechanism. Keywords: Anti-convulsant; 1,5-benzothiazepine; V-Life MDS 4.3.