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Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.
Subject(s)
Animals , Male , Rats , Seizures/chemically induced , Memory Consolidation/classification , Amitriptyline/adverse effects , Pentylenetetrazole/agonistsABSTRACT
Abstract Introduction Systemic administration of pentylenetetrazole (PTZ) causes brain damage (BD), and triggers a series of morphological and neurochemical changes, which in turn bring about behavioral, cognitive, and motor deficits. Serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels are controlled by various brain structures and these levels are related to motor activity; however, the concentration of these neurotransmitters during the postictal process remains unknown. Objective We investigated the concentration of 5-HT, NA and DA in the hippocampus, cerebellum, and cortex on motor deficit during the postictal stage. Method Eighteen male Wistar rats (300 g) assigned to two groups: control (n = 9, saline solution) and experimental (n = 9, PTZ) were used. Myoclonic shakes were counted and motor behavior assessments were recorded during three hours post PTZ injection (90 mg/kg). The cortex, cerebellum, and hippocampus of each rat were dissected to determine the 5-HT, DA, and NA concentration by high performance liquid chromatography. Results PTZ induced a significant increase in total 5-HT and DA levels in the hippocampus and cortex; in the cerebellum there was a significant increase in the concentration of 5-HT and NA. The presence of myoclonic shakes as well as a marked motor deficit in the experimental group were significantly different in comparison to the control. Discussion and conclusion 5-HT modifies the concentration of other monoamines directly involved in motor aspects such as NA and DA in the hippocampus, cerebellum, and cortex during the postictal process.
Resumen Introducción La administración sistémica de pentilentetrazol (PTZ) causa daño cerebral y desencadena una serie de cambios morfológicos y neuroquímicos que a su vez provocan déficits conductuales, cognitivos y motores. Los niveles de serotonina (5-HT), dopamina (DA) y noradrenalina (NA) son modulados por varias estructuras cerebrales y sus concentraciones se relacionan con la actividad motora; sin embargo, se desconoce la concentración de estos neurotransmisores durante el proceso postictal. Objetivo Evaluar la manera en que la concentración de 5-HT, NA y DA en el hipocampo, el cerebelo y la corteza influye en el déficit motor durante la etapa postictal. Método Se utilizaron 18 ratas macho Wistar (300 g), divididas en dos grupos: control (n = 9, solución salina) y experimental (n = 9, PTZ). Se registraron las sacudidas mioclónicas y se evaluó el comportamiento motor durante tres horas después de la inyección de PTZ (90 mg/kg). Se extrajeron la corteza, el cerebelo y el hipocampo de cada rata para determinar la concentración de 5-HT, DA y NA mediante cromatografía líquida de alta resolución. Resultados La administración de PTZ indujo un aumento significativo en los niveles totales de 5-HT y DA en el hipocampo y la corteza; en el cerebelo hubo un aumento significativo en la concentración de 5-HT y NA. Se encontró una diferencia significativa entre el grupo experimental y control con respecto a las sacudidas mioclónicas; asimismo, los animales del grupo experimental mostraron un marcado déficit motor. Discusión y conclusión La 5-HT modula la concentración de otras monoaminas involucradas directamente en aspectos motores tal como NA y DA en el hipocampo, el cerebelo y la corteza durante el proceso postictal.
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Objectives: Ginkgo biloba leaf extract (GBLE) and L-carnitine extract are a commercial product used as a nutraceutic herbal widely. They have antioxidant and reactive oxygen species (ROS) scavenger. This study hypothesized that GB and L-carnitine may have protective effects against pentylenetetrazol (PTZ) induced oxidative damage in kidney in male albino rats. Materials and Methods: A total of 80 male albino rats were equally divided into eight groups (G1, control; G2, GBLE; G3, L-carnitine; G4, Pentylenetetrazole; G5&G6, pre and post treated PTZ with L-carnitine groups respectively; G7&G8, pre and post treated PTZ with GBLE respectively). Results: Serum urea, creatinine, uric acid and cystatin c were significantly increased in PTZ group when compared with control. Also; kidney homogenate MDA and DNA fragmentation were increased when compared with control while, significant decrease in CAT, SOD, GST and TAC in PTZ when compared with control. On other hand pre and post-treatment with L-carnitine and GBLE improved these parameters. Conclusions: The results revealed that; the treatment with L-carnitine improved these parameters more than GBLE and the results of post treatment were better than pre-treatment.
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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.
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Objective To investigate the effects of low dose of gamma knife irradiation on the expression of N-methyl-D-aspartate (NMDA) receptor subunits in cortex and hippocampus of epileptic rats. Methods The rats were randomly divided into 4 groups: control group, GK group, pentylenetetrazole (PTZ) group and GK+ PTZ group. The rats were injected intraperitoneally with PTZ to establish the epileptic models. Gamma knife irradiation was performed on bilateral frontal cortex of rats at a peripheral dose of 15Gy. After irradiation, the changes of the seizure and behaviors were observed and recorded. The rats were killed on the 12th week after irradiation, Immunohistochemstry and western blotting were used to detect the relative expression levels of NMDAR subunits (NR1, NR2A, and NR2B) in the cortex and hippocampus. Results There were no epileptic seizures in the control group and the GK group. Compared with the PTZ group, the epileptic seizures of rats in the GK+PTZ group were significantly reduced after low dose gamma knife irradiation (P<0.05). Compared with control group, the protein expression levels of NR1, NR2A and NR2B in the PTZ group increased significantly in the cortex and hippocampus, and so were the positive neurons and their average absorbance value (P<0.05). Compared with PTZ group, the protein expression levels of NR1, NR2A and NR2B of the GK+PTZ group decreased remarkably in the cortex and hippocampus (P<0.05). Protein expression levels of NR1, NR2A and NR2B were not significantly different between control group and GK group (P＞0.05). Conclusion Epileptic rats exhibited an increase in the protein expression levels of NR1, NR2A and NR2B in the cortex and hippocampus while low dose of gamma knife irradiation can decrease expression levels of NMDA receptor subunits in the cortex and hippocampus of epileptic rats, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.
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Aim: To investigate the phytochemicals and the anticonvulsant activity of the ethanol leaf extract of Culcasia falcifolia used in the traditional medical treatment of epilepsy. Methodology: The phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using Pentylenetetrazole in mice. Result: The preliminary phytochemical screening carried out on the ethanol extract of Culcasia falcifolia revealed the presence of alkaloids, flavonoids, saponins, tannins, polyphenols, and glycosides. In the anticonvulsant activity, there was a significant (*p< 0.05, **p<0.01) increase in the mean latency of tonic convulsion (243.72 ± 6.90*, 402.56 ± 5.52**) and significant (*p< 0.05, **p<0.01) decrease in the mean duration of tonic convulsion (192.62 ± 7.72*, 158.99 ± 8.66**) in a dose-dependent manner at the dose of 200 and 400 mg/kg body wt. respectively. The extract at 400 mg/kg body wt. showed 100% protection against mortality. Conclusion: The results of this study suggest that the ethanol leaf extract of Culcasia falcifolia possesses anticonvulsant activity in PTZ induced seizure in mice.
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Objective: To investigate the effects of sodium valproate (VPA) on the expression of FAK and FAK-pY397 in hippo-campus of rats with seizure induced by pentylenetetrazole (PTZ). Methods: A total of 75 rats were randomly divided into 5 groups:the normal control group, the epilepsy model group (PTZ group) and the VPA groups(150,300 and 600 mg·kg-1·d-1)with 15 ones in each group. The model rats were continuously given PTZ (32 mg·kg-1·d-1) by intraperitoneal injection for 4 weeks and paid close attention to the behavioral changes, and then VPA was administrated orally for 2 weeks. The pathological changes of hippo-campus tissue were observed by HE staining. The expressions and distributions of FAK, FAK-pY397 and integrin in serum and hippo-campus were evaluated by immunohistochemical assay and enzyme-linked immunosorbent assay (ELISA). Results: Compared with the model group, the symptoms of epilepsy in VPA groups were significantly relieved and cell apoptosis was improved. Immunohistochemis-try showed that the expression of FAK-pY397 decreased significantly in VPA groups with the increase of sodium valproate dose, and there was no significant difference in the expression of ITGα3. The VPA groups significantly reduced the expression of FAK, FAK-pY397 and ITGβ1(P<0. 05), the expression of FAK and ITGβ1 protein in peripheral serum decreased significantly (P<0. 05), but the expression of FAK-pY397 did not change significantly. Conclusion: VPA can effectively participate in or affect the process of epi-lepsy by inhibiting the expressions of FAK-pY397 and ITGβ1 in hippocampal tissue of epileptic rats.
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Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus (M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models. Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses (0.1-0.8 mL/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route. Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded. Results: The essential oil at 0.8 mL/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pentylenetetrazole alone, the mortality was 100% within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%-100% died in those that had been pre-treated with the oil. Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.
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Epilepsy is a kind of neurogenic diseases with high prevalence and characterized by seizure, brain paradoxical discharge and convulsion in spontaneous, transient, recurrent and uncontrolled manner. Development of new anti-epilepsy drugs requires a new reliable and high-performance animal models in screening of leading compounds. In this study, an epilepsy model in larval zebrafish was established using pentylenetetrazole (PTZ) compound. The results show that PTZ induced epilepsy-like seizure behavior such as irregular circular swimming, exciting locomotion, high swim velocity and convulsion in zebrafish. Expression patterns of two epilepsy-related gene c-fos and lgi1 were analyzed using RT-PCR and in situ hybridization; c-fos was enhanced and extended and lgi1 expression was reduced in PTZ concentration-dependent in the larval brain. When the model larvae exposed to anticonvulsant valproate (VPA), the epilepsy-like symptom decreased or disappeared, the marker genes c-fos and lgi1, as well as NeuN protein recovered to the normal levels. These responses to PTZ and to antiepileptic drug VPA are consistent with the observations in clinical studies and mouse models. Using this model, we evaluated anti-epilepsy activity of compounds Y53 and BMT, two homolog of berberine. The results show that the model larvae seizure triggered by lighting was partly remedied by Y53; and the larval exciting locomotion under the condition of no stimulation was suppressed by BMT. The findings indicate that the zebrafish larval epilepsy model is able to distinguish compounds with different activities in eleptiform seizure. We conclude that the zebrafish epilepsy model may be as a reliable and useful platform in screening of new anti-epilepsy candidates, which is suitable for basic research in epilepsy pathogenesis.
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Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus (M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models. Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses (0.1–0.8 mL/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route. Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded. Results: The essential oil at 0.8 mL/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pen-tylenetetrazole alone, the mortality was 100%within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%–100%died in those that had been pre-treated with the oil. Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.
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Background: The objective is to evaluate the anticonvulsant activity of nitrendipine in seizure-induced mice. Methods: Albino mice (25-30 g) of either sex were randomly selected and divided into four groups of six mice each. After overnight fasting, Group I received 0.25 ml of propylene glycol and served as the control, Group II received valproic acid (110 mg/kg orally) as standard, Groups III received 5 mg/kg of nitrendipine and 100 mg/kg of valproic acid, Group IV received 5 mg/kg of nitrendipine and 75 mg/kg of valproic acid, and Group V received 5 mg/kg of nitrendipine and 50 mg/kg of valproic acid all of which were administered orally 60 mins prior to the test in this acute study. The anticonvulsant activity was screened using maximal electroshock (MES) model and pentylenetetrazole (PTZ) model. Results: The nitrendipine showed a considerable reduction in the duration of hindlimb extensor phase in MES model and also delayed the latency of seizures induced by PTZ when compared with control group. The probable mechanism of anticonvulsant action of nitrendipine could be due to its interference with the gamma amino butyric acid type aminergic mechanism, modulation of nicotinic, and N-methyl-D-aspartate receptors. Conclusion: Nitrendipine possesses the anticonvulsant activity and has a beneficial role in epilepsy.
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Objectives: The aim of the study was to investigate anticonvulsant effect of Moringa oleifera on maximal electroshock (MES), pentylenetetrazole (PTZ) and pilocarpine induced seizures. Methods: The ethanolic extract of Moringa oleifera leaves (200mg/ Kg) was used to study its anticonvulsant effect on MES, PTZ and pilocarpine induced seizures in Swiss albino mice. Suppression of the tonic hind limb extension, duration of convulsion, abolition of convulsions was noted respectively for the above tests. Results: The ethanolic extracts of Moringa oleifera leaves (200mg/ Kg) significantly (p<0.001) abolished the hind limb extension induced by MES. The same dose also significantly (p<0.001) protected the animals from PTZ induced tonic convulsions. None of the animals treated with same dose of plant extract reached the status epilepticus state in pilocarpine induced seizures. Conclusions: The data suggests that the ethanolic extracts Moringa oleifera leaves may produce its anticonvulsant effect via different mechanisms since it prevented the hind limb extension induced by MES, decreased the duration of convulsions produced by PTZ and abolished status epilepticus in pilocarpine induced seizures.
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Aims & Objectives: To evaluate or screen the anticonvulsant effect of Nicorandil a potassium channel opener in Pentylenetetrazole(PTZ) induced convusions in albino mice. Materials & Methods: Mice of either sex weighing 20-25gms were selected for the present study. The animals were divided into 6 groups with each group consisting of 6 albino mice. Group 1 mice received placebo (0.2ml of distilled water) intraperitoneally (i.p), group 2 received sodium valproate 200 mg/kg/i.p. as positive control, while groups 3,4, 5 and 6 were administered Nicorandil 5, 10, 20 and 40 mg/kg i.p respectively. Pentylenetetrazole (PTZ) was administered in the dose of 100mg/kg i.p, 30mins after Nicorandil/ control drug pre-treatment. Onset and duration of clonic convulsion were recorded. Results: Nicorandil pretreatment in the dose of 5mg/kg increased onset time and significantly decreased the duration of convulsions,while the doses of 10, 20, 40mg/kg prevented the convulsions. Conclusion: Nicorandil possesses significant anticonvulsant activity comparable to sodium valproate on PTZ induced seizure in albino mice.
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Objective To investigate the effect of zonisamide as a new antiepileptic drug on nitric oxide (NO) content and nitric oxide synthase (NOS) activity in serum and brain tissue of epileptic rats. Methods Eight healthy rats were used as normal control group, and twenty-four epileptic rats induced by pentrazol were randomly divided into epilepsy model group, zonisamide group and phenobarbital group. Levels of NO and malondialdehyde (MDA) content, NOS and superoxide dismutase (SOD) activity in serum and brain tissue were detected in four groups. Results Forty-two rats were injected pentrazol, and 35 (83%) rats were established the rat model successfully. Epileptic waves were visible in EEG of epileptic rats. The concentrations of NO, MDA and the activity of NOS in serum and brain were significantly increased, the activity of SOD was significantly decreased, in epileptic rats than those of control rats. The concentrations of NO and MDA were significantly increased; the activity of SOD was significantly decreased, in brain in phenobarbital group compared with those of control group. There were significantly lower levels of NO, MDA and NOS, and significantly higher level of SOD in serum and brain tissue in zonisamide group and phenobarbital group than those of epileptic model group (P＜0.05). Conclusion Zonisamide plays an antiepileptic role by reducing the concentration of NO in brain of epileptic rats.
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Aim To observe histopathological changes of hippocampus after acute epilepsy induced by penty-lenetetrazole (PTZ)in rats.Methods Five groups as control group,PTZ-induced 24 hours(h)group,PTZ-induced 72 hours group,PTZ-induced 1 20 hours group and PTZ-induced 1 44 hours group were designed.PTZ (64 mg·kg -1 )was administered with a single intrap-eritoneal injection for generalized tonic-clonic sei-zures in the current experiment.Control and PTZ trea-ted animals were sacrificed after specific time points. Brain was dissected out and then evaluated for neuro-pathological changes using Nissl staining and immuno-histochemical technique.Results In this study PTZ-induced hippocampal neuron status apoptosis occurred at 24 hours and was sustained for 1 44 hours after status epilepticus.Whereas,activated caspase-3 and AIF ap-peared at 24 hours and were sustained for 1 44 hours af-ter status epilepticus.Conclusion The results of this study show that the significant histopathological chan-ges of hippocampus appear in the vicinity of 1 20 hours after intraperitoneal injection of pentylenetetrazole.
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A new series of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ)-evoked convulsion model and antidepressant activity in the forced swimming test (FST) model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q) showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine.
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Geraniol (GR) is an acyclic monoterpene alcohol present in essential oils of aromatic plant species used in Brazilian folk medicine for the treatment of epilepsy. The present study was designed to evaluate the anticonvulsant effect of GR and of the inclusion complex geraniol:beta-cyclodextrin (GR:beta-CD). Mice were treated with GR or with GR:beta-CD (50, 100 and 200 mg/kg) 30 min before pentylenetetrazole (PTZ) or strychnine (STN). GR at 200 mg/kg and GR:beta-CD at the doses of 100 and 200 mg/kg significantly increased the latency for the first PTZ-induced convulsion and reduced the percentage of animals that convulsed. The pretreatment of flumazenil did not revert the anticonvulsant effect of GR in the PTZ-induced convulsion model. In the STN-induced convulsion model, the effects of GR were investigated and no difference was found against control. The results demonstrated an anticonvulsant activity of GR in the PTZ-model, which was potentialized by the complexation with beta-CD...
Geraniol (GR) es un alcohol monoterpeno acíclico presentes en los aceites esenciales de las especies de plantas aromáticas utilizadas en la medicina popular brasileña para el tratamiento de la epilepsia. El presente estudio fue diseñado para evaluar el efecto anticonvulsivo del GR y de la inclusión de geraniol complejo: beta-ciclodextrina (GR:beta-CD). Los ratones fueron tratados con GR o con GR:beta- CD (50, 100 y 200 mg/kg) 30 minutos antes de pentylenotetrazole (PTZ) o strichinine (STN). GR a 200 mg/kg y GR:beta-CD en las dosis de 100 y 200 mg/kg aumentó significativamente la latencia para la primera convulsión inducida PTZ-y redujo la porcentaje de animales que convulsionó. El tratamiento previo de flumazenil no revirtió el efecto anticonvulsivo de GR en el modelo de convulsión inducida con PTZ. En el modelo de convulsión inducida com STN, los efectos de GR fueron investigados y no se encontró ninguna diferencia contra el control. Los resultados demostraron una actividad anticonvulsiva de geraniol en el modelo de PTZ, que fue potenciada por la formación de complejos con beta-CD...
Subject(s)
Animals , Mice , Oils, Volatile/administration & dosage , Anticonvulsants/administration & dosage , Epilepsy/drug therapy , Terpenes/administration & dosage , Cyclodextrins , Neuroprotective Agents/administration & dosage , Monoterpenes/administration & dosage , Pentylenetetrazole/administration & dosageABSTRACT
Background: Abelmoschus moschatus is an aromatic and medicinal plant, used as traditional medicine in the Thirunelveli district and distributed in many parts of Asia, including India. The present study was aimed to evaluate central nervous system (CNS) activities of ethanolic seed extract of A. moschatus (AEAM). Methods: Oral administration of AEAM at doses of 200 and 400 mg/kg on various behavioral models forced swim, tail suspension, light-dark box, hole-board, elevated-plus-maze, locomotor, strychnine, maximal electroshock induced seizure, pentylenetetrazole (PTZ), rotarod, climbing an inclined screen models were utilized. Results: In the open field test, AEAM (200 and 400 mg/kg) increased the numbers of rearing. However, the number of central motor and ambulation were reduced. The number of entries and the time spent in the open arm were increased, whereas the number of locomotion was decreased (p<0.001) in elevated-plus-maze and actophotometer test, respectively. AEAM (200 and 400 mg/kg) protected the mice against the PTZ and strychnine-induced convulsions; it causes significant dose-dependent increase in latency of convulsion. Treatment with AEAM reduced the duration of the tonic hind limb extension, increased the hypnotics time and decreased motor co-ordination of experimental animals. Conclusion: This study concludes A. moschatus is an alternative source for CNS drug development.
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Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetrazole (PTZ) method. Methods: Adult male albino mice were divided into four different groups of six animals each and anti-epileptic activity was assessed using MES method and PTZ method. Group I acted as a control, Group II received any one of the four AEDs (phenytoin, CBZ, phenobarbitone or sodium valproate) in sub-effective doses, Group III received diazepam or clonazepam alone, Group IV received a combination of diazepam or clonazepam with any one of the AEDs. Results: In MES method, the groups receiving combination of diazepam with phenytoin and CBZ showed significant protection compared to the control group (p<0.01 and p<0.02), respectively. However, diazepam in combination with sodium valproate and phenobarbitone did not show any significant protection compared to the control group and individual antiepileptic group. All the four antiepileptic showed significant protection against MES seizure in combination with clonazepam when compared to control group. In PTZ method, combination of sodium valproate with clonazepam showed significant protection compared to control group (p<0.02). However, this was not observed with diazepam-valproate combination. Conclusion: Clonazepam potentiates the action of all the four anti-epileptics while diazepam potentiates only phenytoin and CBZ against MES seizures. Clonazepam but not diazepam potentiates the action of sodium valproate against PTZ seizures.
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Citrus maxima is a traditional medicine used to treat astringent, constipation, hypnotic, inflammation and antiseptic. Therefore, we aimed to evaluate central nervous system activities of ethanolic extract of Citrus maxima (EECM). Oral administration of 200 and 400 mg/kg of EECM was to the depressant, anxiolytic, convulsant, hypnotic and muscle relaxant experimental animals. In the locomotor test, EECM increased the numbers of rearing, central motor and ambulation were reduced. The number of entries and time spent in the open arm was increased, decreased locomotion in elevated-plus-maze and actophotometer test. EECM protected the mice against the pentylenetetrazole and strychnine induced convulsion in a dose dependent manner. Treatment with EECM (p<0.01) reduced the duration of the tonic hind limb extension, increased hypnotics time and decreased motor co-ordination of experimental animals. This study concludes C. maxima will be an alternative source for psychiatric and neurological disorders.