Phytochemical and anticonvulsant screening of three medicinal plants used in the treatment of epilepsy in the south-western part of Nigeria

The burden of epilepsy in developing countries made medicinal plants like Xylopia aethiopica fruit; Khaya grandifoliola, Alstonia boonei etc an alternative source in epilepsy management in the south-western part of Nigeria. The aim of the study was to provide pharmacological rationale for the ethnomedicinal use of the plants in epilepsy management. The oral medial lethal dose of methanol stem bark extracts of Alstonia boonei (MEAB) and Khaya grandifoliola (MEKG) and methanol fruit extract of Xylopia aethiopica (MEXAF) were done in accordance with the Organization for Economic Cooperation Development guideline. Quantitative and qualitative phytochemical profiling of the extracts was done. Anticonvulsant screening was carried out on the extracts (doses: 75, 150 and 300 mg/kg) using the pentylenetetrazole (PTZ)-induced seizure and maximum electroshock tests (MEST). Results showed that the MEXAF has the highest amount of phytochemicals except for saponins in MEKG; and MEAB with the least amount (but higher alkaloid) than MEKG. The TLC showed different bands of spots of the extracts. In the PTZ test, MEXAF showed 100 % protection against mortality at 300 mg/kg; MEAB with 66.67 % protection at 75 mg/kg and MEKG 0 % protection. MEAB, MEKG and MEXAF nonsignificantly increased the onset of seizure and latency to death. In the MEST, MEXAF, MEKG and MEAB at 75 mg/kg protected 50, 33.3 and 16.67% of the animals against tonic hind limb extension respectively and nonsignificantly (p˃0.05) decreased the recovery time at a dose of 75 mg/kg. It was concluded that the extracts possess anticonvulsant activities hence, the pharmacological credence for the ethnomedicinal use of these plants in treating epilepsy.

Evaluation of the Anticonvulsant and Antidepressant Effects of the Aqueous Extract of the Leaves of Ascotheca paucinervia (T. Anderson ex C.B. Clarke) Heine in Mice

The present study was undertaken to evaluate the anticonvulsant and antidepressant effects of Ascotheca paucinervia leaves on mice by using strychnine at 2.5mg/kg to induce convulsions and the forced swimming test to create a stressful situation, respectively. Concerning convulsions, only the 500mg/kg extract significantly increases (p<0.001) the time to onset of convulsions and it non-significantly reduces the duration of convulsions induced by strychnine. In addition, the extract reduces very significantly in a dose-dependent manner the time of immobility and it significantly increases the swimming time as well as the climbing time at both doses. At the same time, the estimation of the acute toxicity of the extract from the leaves of Ascotheca paucinervia according to guideline No. 425 of the OECD (2022) shows that the latter is weakly toxic and its LD50 is greater than 5000mg/kg. In addition, the evaluation of the sedative effect of this extract shows that it produces a dose-dependent sedative effects and at doses of 250m/kg and 500mg/kg, the extract significantly potentiates the sleep induced by phenobarbital. In summary, the results obtained suggest that Ascotheca paucineervia leaves extract possesses anticonvulsant and antidepressant effects.

Practical considerations in the pharmacological treatment of bipolar disorder / 四川精神卫生

Bipolar disorder is one of the most common mood disorders characterized by an early age of onset and high prevalence rate， and patients tent to have poor prognosis due to high misdiagnosis rate and incomplete diagnosis rate. At present， existing pharmacological treatment for bipolar disorder remains highly variable. Therefore， this paper presents a review of indications of the medications， clinical therapeutic effect and adverse drug reactions， thus providing references for the pharmaceutical treatment of bipolar disorder.

Anticonvulsant drug regimen and cost of acute treatment for status epilepticus in a Philippine tertiary hospital: A retrospective cohort study

Background@#Status epilepticus (SE) is a neurological emergency requiring prompt evaluation and management to prevent disease refractoriness associated with significant mortality and morbidity. Thus, estimating costs attributable to the treatment of SE is important because of the severity of this disease. In the Philippines, healthcare provisions are mostly out-of-pocket expenses; hence the cost of treatment is a critical determinant for disease management. Unfortunately, the availability of data regarding the cost of illness of SE in developing countries is limited.@*Objectives@#To determine the frequently used anticonvulsant drug regimen and direct inpatient costs of acute treatment for status epilepticus within five years in a private tertiary hospital in the Philippines.@*Methods@#Records from patients diagnosed with SE who were admitted under or referred to the Adult Neurology Service in a private tertiary hospital from January 2015 to December 2019 were retrospectively evaluated. The SE type was classified as non-refractory (NRSE), refractory (RSE), and super refractory (SRSE). Demographic data, clinical features, SE type, etiology, antiepileptic drugs (AEDs) and anesthetic drugs used, total cost of AEDs and anesthetic drugs, total cost of 5-day hospitalization, and total cost of entire length of stay were recorded.@*Results@#We retrieved the records of 61 patients admitted for SE. Of these patients, 23 were classified as nonrefractory, 20 as refractory, and 18 as super refractory. Diazepam was given to all SE patients as first-line treatment. Valproic acid and levetiracetam were used as second-line treatments. The most frequently given anesthetic drug was midazolam. The mean hospitalization cost per patient was ₱52,0982.3 for SE, ₱659,638.7 for RSE, and ₱134,1451 for SRSE. The mean cost of 5-day hospitalization was ₱193,572.3 for NRSE, ₱358,808.5 for RSE, and ₱652,781 for SRSE. The mean cost of medications was ₱18,546 for NRSE, ₱30,780 for RSE, and ₱128,263 for SRSE.@*Conclusion@#The direct cost of SE varied depending on subtype and response to treatment. Costs increased with disease refractoriness. Direct inpatient treatment costs for SRSE were twice as high as that of NRSE and RSE.

Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice / Efeitos anticonvulsivantes da desvenlafaxina na modulação da monoamina cerebral e do estresse oxidativo em camundongos

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P < 0,01) e o LPO reduziu significativamente (P < 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.

Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice

Abstract Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P 0.01) increased and LPO reduced significantly (P 0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

Resumo O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P 0,01) e o LPO reduziu significativamente (P 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.

Non-surgical periodontal treatment for drug-influenced gingival enlargement: a four-year follow-up case report

ABSTRACT: Drug-influenced gingival enlargement is considered to be an important side effect related to the use of some medications and often produces important esthetic changes for patients, as well as clinical symptoms such as pain, bleeding, abnormal tooth movement and occlusion problems. Anticonvulsants, immunosuppressants and antihypertensive drugs have been reported as the main inducers of these periodontal disorders. This case report describes the 4-year clinical follow-up of a young patient with a history of excessive gingival enlargement as a consequence of drug therapy for epilepsy (phenytoin and phenobarbital); the nonsurgical periodontal treatment of the excessive gingival enlargement was associated with the replacement of the patient's epilepsy medications with valproic acid. We conclude that intensive mechanical control of bacterial biofilms, instruction on oral hygiene guidelines and behaviors and the substitution of alternative anticonvulsant medications are the best way to control the drug-influenced gingival enlargement.

Anticonvulsivantes y su efecto en el metabolismo de la vitamina D: revisión del tema, a propósito de un caso / Anticonvulsants and their effect on the metabolism of vitamin D: literature review with case report

La epilepsia es una enfermedad neurológica frecuente que afecta a cerca de 50.000 millones de personas en el mundo. En Chile, la prevalencia estimada es de 10.8 a 17 por 1.000 habitantes. La primera opción para su tratamiento son los fármacos antiepilépticos (FAE) los cuales logran un aceptable control de enfermedad en la mayoría de los casos, sin embargo, tienen la potencialidad de desencadenar una serie de efectos adversos destacando entre ellos el desarrollo de hipocalcemia (HC) secundaria a hipovitaminosis D (HD), alteración que por lo general es leve y asintomática. Presentamos el caso de una mujer perimenopausica con antecedente de epilepsia en tratamiento con anticonvulsivante que desarrolla hipocalcemia severa. Además revisamos los mecanismos descritos a través de los cuales los FAE afectan el metabolismo de esta vitamina.

Epilepsy is a common neurological disease that affects about 50,000 million people in the world. The estimated prevalence is 10.8 to 17 per 1.000 inhabitants in Chile. The first option for its treatment are antiepileptic drugs (AEDs) which achieve an acceptable control of the disease in most cases, however, they have the potential to trigger a series of adverse effects (AE) highlighting among them the development of hypocalcemia (HC) secondary to hypovitaminosis D (HD), an alteration that is generally mild and asymptomatic. We present the case of a perimenopausal woman with a history of epilepsy under treatment with an anticonvulsant who develops severe hypocalcemia. We also review the mechanisms described through which AEDs affect the metabolism of this vitamin.

Ethanolic Extract of the Red Algae Meristiella echinocarpa (Areschoug) Confers Neuroprotection in Mice / Extrato Etanólico da Alga Vermelha Meristiella echinocarpa (Areschoug) Confere Neuroproteção em Camundongos

Objectives: This study aimed to investigate the neuroprotective effects of the ethanolic extract obtained from red algae marine Meristiella echinocarpa (Areschougiaceae) ­ EEMe. Methods: EEMe was used in doses ranging from 10 to 40 mg/kg, administered intraperitoneally in mice. Behavioral tests were performed to assess locomotor activity (open field), anxiety (elevated plus maze), depression (tail suspension), and motor coordination (rota-rod). The anticonvulsant effect of the algae extract was evaluated in two models of seizures induced by strychnine and pentylenetetrazol. The level of oxidative stress was also evaluated in the following brain areas: the prefrontal cortex, hippocampus, and striatum. Statistical analysis was performed applying ANOVA followed by the Bonferroni test. Results: EEMe reduced significantly the number of crossing (36%) and rearing (54%) in the open field test and increased 1.3x the immobility time in the tail suspension test. In brain areas EEMe also reduced significantly malondialdehyde levels (striatum: 45%, hippocampus: 38%, prefrontal cortex: 37%) and nitrite levels (striatum: 72%, hippocampus: 79%, prefrontal cortex: 63%), and increased the reduced-glutathione levels (striatum: 72%, hippocampus: 73%, prefrontal cortex: 42%). In addition, the extract significantly prolonged the latency of seizures induced by strychnine (38%) or pentylenetetrazol (57%), and the latency of death induced by pentylenetetrazol (6.1x). Conclusion: EEMe exhibits antioxidant and anticonvulsant effects, probably involving GABAergic and glycinergic pathways.

Objetivos: este estudo teve como objetivo investigar os efeitos neuroprotetores do extrato etanólico da alga marinha vermelha Meristiella echinocarpa (Areschougiaceae) - EEMe. Métodos: EEMe foi utilizado em doses que variaram de 10 a 40 mg/kg, administrados via intraperitoneal em camundongos. Foram realizados testes comportamentais que avaliaram a atividade locomotora (campo aberto), a ansiedade (labirinto em cruz elevado), a depressão (suspensão em cauda) e a coordenação motora (rota-rod). O efeito anticonvulsivante do extrato da alga foi avaliado em dois modelos de convulsões por estricnina e pentilenotetrazol. Foi também realizada a avaliação do nível de estresse oxidativo nas seguintes áreas cerebrais: córtex pré-frontal, hipocampo e corpo estriado. A análise estatística foi realizada, aplicando a ANOVA seguida do teste de Bonferroni. Resultados: o EEMe reduziu, significativamente, o número de cruzamentos (36%) e o número de rearing (54%) no teste de campo aberto e aumentou, em 1,3x, o tempo de imobilidade no teste de suspensão pela cauda. Nas áreas cerebrais, o EEMe também reduziu, significativamente, os níveis de malondialdeído (estriado: 45%, hipocampo: 38%, córtex pré-frontal: 37%) e os níveis de nitrito (estriado: 72%, hipocampo: 79%, córtex pré-frontal: 63%) e aumentou a glutationa reduzida (estriado: 72%, hipocampo: 73%, córtex pré-frontal: 42%). Além disso, o EEMe prolongou, significativamente, a latência das convulsões induzidas por estricnina (38%) ou pentilenotetrazol (57%), e a latência da morte induzida por pentilenetetrazol (6,1x). Conclusão: o EEMe apresenta efeitos antioxidantes e anticonvulsivantes, provavelmente envolvendo as vias GABAérgica e glicinérgica.

Síndrome de DRESS asociado al uso de anticonvulsivantes / DRESS syndrome associated to the use of anti-convulsiveness

Introducción: El síndrome Drug Reaction with Eosinophilia and Systemic Symptoms - DRESS, constituye una grave reacción adversa a medicamentos, principalmente a fármacos anticonvulsivantes. Objetivo: Describir la evolución clínica de un síndrome de DRESS en una paciente atendida en el Hospital Militar Central "Dr. Luis Díaz Soto". Caso Clínico: Paciente femenina de 27 años de edad con antecedentes patológicos personales de epilepsia. Tres meses luego de iniciada terapia con difenilhidantoína aparece fiebre, exantema maculopapular que progresa a eritrodermia exfoliativa, signos de daño hepático, adenopatías cervicales y eosinofilia. Se diagnosticó síndrome de DRESS secundaria al uso de anticonvulsivantes. Conclusiones: La evolución clínica resultó favorable, luego de la retirada del fármaco y la aplicación de esteroides por vía oral(AU)

Introduction: Drug Reaction with Eosinophilia and Systemic Symptoms - DRESS, syndrome constitutes a serious adverse reaction to medications, mainly anticonvulsant drugs. Objective: To describe the clinical evolution of DRESS syndrome in a patient treated at the Hospital Militar Central "Dr. Luis Díaz Soto". Case Report: 27-year-old female patient with a personal pathological history of epilepsy. Three months after initiation of diphenylhydantoin therapy, fever appeared maculopapular rash that progressed to exfoliative erythroderma, signs of liver damage, cervical adenopathies and eosinophilia. DRESS syndrome was diagnosed secondary to the use of anticonvulsants. Conclusions: The clinical evolution was favorable, after the withdrawal of the drug and the application of steroids orally(AU)

Efficacy, Tolerability and Serum Phenytoin Levels after Intravenous Fosphenytoin Loading Dose in Children with Status Epilepticus

Objective: To evaluate the efficacy and tolerability of intravenousfosphenytoin in children with status epilepticus, and resultingserum total phenytoin levels.Methods: In this prospective study, 51 children aged less than 18years received intravenous loading dose of fosphenytoin (18-20mg/kg). Serum total phenytoin levels were estimated at 90 -100minutes. Outcomes studied were (i) seizure control and local and/or systemic adverse effects in next 24 hours and (ii) phenytoinlevels and its correlation with dose received, seizure control andadverse effects.Results: The actual dose of fosphenytoin received varied from15.1 to 25 mg/kg. Seizures were controlled in 45 (88%) childrenand, two required additional dose of 10 mg/kg. None of thechildren showed any local or systemic adverse effects. Serumtotal phenytoin levels were in the therapeutic range (10-20 μg/mL)in 12 (23.5%), sub-therapeutic in 16 (31.3%) and supra-therapeutic in 25 (49%) children. There was weak correlation ofthe phenytoin levels with dose of fosphenytoin received, seizurecontrol, or adverse effects.Conclusion: Intravenous fosphenytoin loading dose of 20 mg/kgis effective in controlling seizures in 88% of children with statusepilepticus, with a good safety profile. Seizure control and adverseeffects appear to be independent of serum total phenytoin levelsachieved.

Design and Synthesis of New Derivatives of (E)-3-(5-((phenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one for their Anticonvulsant Potential

Objective: The objective of the paper was to design and synthesize new derivatives of ((E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one and evaluated for their anticonvulsant potential. Materials and Methods: Various synthesis of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one derivatives has been synthesized by reacting 2-substituted benzoxazin-4-one with (E)-2-(4-Substituedstyryl)-4H-benzo[d] [1,3]oxazin-4-one. All synthesized compounds have been characterized by the infrared, 1HNMR, and mass spectral analysis. Proposed compounds have been evaluated for anticonvulsant potential by subcutaneous pentylenetetrazole and maximal electroshock seizure model and compared with the reference drug phenytoin and carbamazepine. Neurotoxicity study of the synthesized compounds was also performed. Results and Discussion: The anticonvulsant evaluation of synthesized compound QNM-1, QNM-2, QNM-4, QNM-6, QNM-9, QNM-11, QNM-13, and QNM-15 has shown seizure protection at 100 mg/kg dose after 30 min and 4 h, so they have good onset of action as quickly reach brain and have prolonged action reveal that compound metabolized slowly. Whereas compound QNM-7, QNM-8, and QNM-12 were moderate active and reveal that their high concentration is required to cross blood brain barrier. Compounds QNM-3, QNM-5, QNM-10, and QNM-14 were less active. Compounds having chlorine, bromine, fluorine, and nitro in the phenyl moiety have shown good activity when attached to para group but the addition of meta and ortho group of the same may provide least active compounds and in last fluorine compounds have shown comparative less active compounds. Conclusion:The Pharmacological evaluation suggest that eight synthesized compounds have shown promising anticonvulsant potential and bulkier compounds can easily penetrate BBB to exert their effect.

Anticonvulsant activity of nicardipine in experimentally induced seizures in wistar albino rats.

Background: The objective of the study was to evaluate the anticonvulsant activity of nicardipine in wistar albino rats.Methods: Anticonvulsant activity of nicardipine in a dose 10 mg/kg, and its effect with the standard drug lamotrigine (5 mg/kg) was studied in a maximal electroshock seizures (MES) experimental animal model.Results: Nicardipine in dose of 10 mg/kg showed significant anticonvulsant effect (p<0.001) and combination with standard drug lamotrigine (p<0.001) also showed more significant anticonvulsant effect in MES model.Conclusions: Nicardipine is having anticonvulsant activity and it also potentiates the anticonvulsant effect of lamotrigine in MES model.

Evaluation Of Anticonvulsant Activity Of Cow Urine Betel Vine Extract In Mice

The present study was designed to investigate the anticonvulsant activity of Cowurine betel vine extract in rats. Anticonvulsant activity was performed by using the two modelsMaximal Electric Shock (MES) induced convulsions and Pentylene tetrazole (PTZ) inducedconvulsions. The animals were fed with Cow urine betel vine extract at the dose of 250 and500mg/kg b.w orally for a period of 14 days. The pretreated extract reduced the convulsions ina dose dependent manner which was determined by taking the duration of flexion, extensor,clonus and stupor phase and Percentage of inhibition of seizures relative to controls wascalculated.

Antioxidant and Anticonvulsant Effect of Dennettia Tripetala on Rat Model of Isoniazid-induced Seizure

Aims: This study aimed at investigating the antioxidative, anticonvulsive and histological effects of ethanolic fruit extract of Dennettia tripetala on the pre-frontal lobe of the brain in isoniazid-induced (300 mg/kg, i.p) seizure in adult wistar rat. Introduction: Neuronal hyper-excitability and excessive production of free radicals have been implicated in the pathogenesis of a considerable range of neurological disorders, including epilepsy. The high rate of oxidative metabolism, coupled with the low antioxidant defenses and the richness in polyunsaturated fatty acids, makes the brain highly vulnerable to free radical damage. Study Design: This is an original research conducted in Department of Anatomy, Faculty of Basic Medical Sciences, Enugu State University of Science and Technology (ESUT), Parklane, Enugu State, Nigeria, between June and August, 2019. Methodology: A total number of twenty four wistar rats were used for this experiment, the animals were grouped into six groups with four animals per group, Group I served as the negative control, Group II served as the positive control, Group III received the standard drug as well as the Isoniazid, while group IV, V and VI were treated with ethanolic extract of Dennettia tripetala at different dosages; 250 mg/kg, 500 mg/kg and 750 mg/kg, intraperitoneally (i.p) respectively and its effects compared with a standard drug (Pyridoxine) treated group. Results: The extract significantly prolonged the onset of seizure at high dose administration (750 mg/kg) but completely prevented seizure occurrence at low and medium dose administration (250 mg/kg and 500 mg/kg, i.p) when induced with isoniazid (300 mg/kg, i.p.). Conclusion: The results obtained from this work suggest that ethanolic extract of Dennettia tripetala has anticonvulsant activity, and this supports the use of the formulation traditionally in the treatment of convulsions, thus should be considered for clinical trials.

Correlation of serum magnesium levels in eclampsia with pritchard and single dose magnesium sulphate regimen

Background: Magnesium sulphate is anticonvulsant of choice for eclampsia. Single dose magnesium sulphate therapy was tried for the management of Eclampsia and Imminent Eclampsia considering the low body mass index of Indian population.Methods: A prospective interventional study comprising of total 80 patients having either eclampsia or imminent eclampsia, to whom the Pritchard or a single dose MgSO4 was given alternatively in a tertiary hospital   from October 2014 to October 2017. Serum magnesium levels, maternal and perinatal outcome and recurrence of convulsions were evaluated using Student- t test and chi square test.Results: Mean Serum Magnesium levels in eclampsia and imminent eclampsia group at 0 min, 30 min, 4 hours in Pritchard regimen were 1.96mg/dl, 5.85mg/dl, 4.68mg/dl while in single dose regimen it was 1.78mg/dl, 462mg/dl, 3.63mg/dl respectively. Those who received Pritchard regimen showed higher level of Serum magnesium levels at 30 minutes and 4 hours than those receiving single dose. By applying T-test it was found that there is a significant difference in serum magnesium levels range in both group but no statistical difference in the control of convulsions in both groups.Conclusions: With increased and almost widespread use of magnesium sulfate in obstetrics there has been concerns regarding its safety. In the study, although P-values are not significant because of small sample size, there is considerable difference in serum magnesium levels 30 min and 4 hours, recurrence of convulsions and maternal morbidity between Pritchard regimen and single dose regimen. The goal which was achieved with Pritchard regimen previously, now can be achieved with single dose regimen in Indian women. Single dose magnesium sulphate is safe and effective in controlling convulsions with improved maternal and perinatal outcome.

Assessment of Morus alba (Mulberry) leaves extract for anti-convulsant property in rats

Background: The mulberry tree, a plant of the family Moraceae and the genus Morus, has been widely cultivated to feed silkworms. Various parts of Morus alba linn used as an Anti-inflammatory, hypoglycemic, cardioprotective, hepatoprotective, free radical scavenging activity and neuroprotective agent. The plant contains flavonoids, moranoline, albanol, morusin coumarine, and stilbene, which have. In this study, anticonvulsant property of Morus alba leaves extract (MAE) was evaluated by using MES and PTZ induced convulsion in rats.Methods: Effects of MAE were evaluated in experimental models of electro convulsions, maximal electro shock (MES) and chemoconvulsion induced by pentylenetetrazole (PTZ) in rats (n=6), which were treated intraperitonially with doses of 100, 200 and 400mg/kg.Results: The duration of tonic hind limb extension (seconds) with MAE in MES induced convulsions at dose of 100, 200, 400 mg/kg is 8.33�21, 6.83�16 & 3.16�98 respectively. In the dose of 400 mg/kg of MAE showed highly significant results by reducing the duration of tonic hind limb extension in MES induced convulsions. And onset of jerky movements (seconds) with MAE in PTZ induced convulsions at dose of 100, 200, 400mg/kg is 157.83�99, 195.66�.02 and 295.50�.10 respectively. In the dose of 400mg/kg of MAE showed highly significant results by delaying the onset of convulsions.Conclusions: Results indicate that the MAE have anticonvulsant effects in MES induced convulsions and in PTZ induced convulsions.

Synthesis and anticonvulsant activity of 6-methyl-2-thioxo-2, 3-dihydropyrimidin-4(1H)-one acetamides

This research aimed at synthesizing new potential anticonvulsants in the series of 2-(4-methyl-6-oxo-1,6-dihydropyrimidin2-yl)thio-acetamides. An initial intermediate 6-methyl-2-thioxo-2,3-dihydro-pyrimidin-4(1Н)-one was obtained by thereaction of thiourea with an acetoacetic ester in the presence of sodium methoxide. The target 2-(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl) thioacetamides were synthesized by alkylation of initial 6-methyl-2-thiopyrimidin-4-one withcorresponding 2-chloroacetamides in Dimethylformamide (DMF) in the presence of potassium carbonate. The structureof compounds was confirmed by 1H Nuclear magnetic resonance (NMR)-spectroscopy, LCMS, and elemental analysis.A screening of anticonvulsant activity of synthesized compounds was carried out using the pentylenetetrazole- andmaximal electroshock-induced seizures models. In these studies, the highest anticonvulsant activity demonstrated acompound 5.5 2-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio]-N-(4-bromophenyl)-acetamide, which decreased thelethality, the number and the severity of seizures, and increased their latent period. For these compound parameters ofЕD50, acute (LD50) and neurotoxicity (TD50), as well as therapeutic (TI) and protective (PI) indexes were determined.Logical structure analysis of anticonvulsant activity screening revealed some patterns of “structure–activity” relationship.

Docking studies of biologically active substances from plant extracts with anticonvulsant activity

Virtual screening methods are promising and useful to design new herbal remedies to satisfy the numerous clinicalneeds. Major problem for extensive use of herbs is the lack of information concerning mechanisms of their action.In the previous pharmacological studies using different models of seizures, it was found that some members of theSolanaceae, Fumariaceae, Lamiaceae, Oleaceae, Viscaceae, and Betulaceae families show a high level of anticonvulsantproperties but the role of individual components of these herbs in the realization of antiepileptic activity remainsunknown. The aim of the present research was molecular docking of compounds identified in the studied herbs to findthe binding mechanism with the suitable targets. The study resulted that the given herbal individual substances did notshow any potential anticonvulsant properties. Anticonvulsant activity of the studied herbs is probably due to the factthat in contrast to individual substances they are characterized by a complex chemical composition and synergism ofbiologically active compounds.

Evaluation of anticonvulsant activity of aqueous extract of Adhatoda vasica leaves by MES model in rats

Background: Epilepsy is the commonest neurological condition affecting people of all ages, race and social class. The present study was taken up to evaluate the anticonvulsant effect of aqueous extract of leaves of Adhatoda vasica in rats. To evaluate the effect of aqueous extract of Adhatoda vasica leaves on maximal electroshock model in albino rats and to compare the effect of aqueous extract of Adhatoda vasica leaves with standard dose of Phenytoin on Maximal electro shock model.Methods: Anticonvulsant activity of aqueous extract of Adhatoda vasica was analysed using MES (Maximal electroshock) model. Phenytoin (25mg/kg) as standard for Maximal electroshock, and two doses of aqueous extract of Adhatoda vasica (100mg/kg and 200mg/kg) were used as test drugs. Parameters observed in MES were abolition of hind limb tonic extension (HLTE) and time taken to regain righting reflex.Results: In MES model, control group showed 0% protection and standard phenytoin group showed 100% protection. Aqueous extract of Adhatoda vasica at 100mg/kg and 200mg/kg showed 33.33% and 50% protection from seizures respectively. The mean duration of time to regain righting reflex was significantly reduced in Adhatoda vasica groups when compared to control group (p <0.001). When groups 100mg/kg and 200mg/kg of Adhatoda vasica were compared for mean difference in the duration of time to regain righting reflex, statistically non-significant results (p >0.05) were obtained.Conclusions: Aqueous extract of leaves of Adhatoda vasica has shown significant anticonvulsant action in MES model.