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Anticonvulsants, anti-epileptics

Gollapalle L Viswanatha, Marikunte V Venkataranganna, Nunna Bheema Lingeswara Prasad, Godavarthi Ashok
OBJECTIVES: This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. MATERIALS AND METHODS: Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions...
September 2016: Journal of Intercultural Ethnopharmacology
Zohreh Ghotbeddin, Mahyar Janahmadi, Ali Yadollahpour
Epilepsy affects about 1-2 % of world population as a chronic neurological disease that is manifested by repeated and consecutive seizures (Grone and Baraban, Nat Neurosci 18(3):339-343, 2015). There is no definitive therapy for epilepsy and antiepileptic drugs cannot offer a permanent and definitive cure for epilepsy, and most epileptic patients become drug resistant (Sasa, J Pharmacol Sci 100(5):487-494, 2006). Surgery and removal of the epileptic focus is a substitute method for treating drug-resistant patients and epilepsy surgery of either side of the brain improves seizure control...
August 26, 2016: Neurological Sciences
Theresia Monica Rahardjo, Tinni Trihartini Maskoen, Ike Sri Redjeki
BACKGROUND: Recovery from cytomegalovirus meningoencephalitis with brain stem death in an immunocompetent patient is almost impossible. We present a remarkable recovery from a possible cytomegalovirus infection in an immunocompetent man who had severe neurological syndromes, suggesting brain stem death complicated by pneumonia and pleural effusion. CASE PRESENTATION: A 19-year-old Asian man presented at our hospital's emergency department with reduced consciousness and seizures following high fever, headache, confusion, and vomitus within a week before arrival...
2016: Journal of Medical Case Reports
M A Lane, C A Kahlenberg, Z Li, K Kulandaival, K L Secore, V M Thadani, K A Bujarski, E J Kobylarz, D W Roberts, T D Tosteson, B C Jobst
OBJECTIVE: A transient decrease in seizure frequency has been identified during therapeutic brain stimulation trials with stimulator in patients in the inactive sham group. This study was performed to examine whether the implantation of intracranial electrodes decreases seizure occurrence and explores factors that may be associated. METHODS: A retrospective review of 193 patients was performed, all evaluated with both scalp video EEG monitoring and intracranial EEG (iEEG) monitoring...
August 16, 2016: Acta Neurologica Scandinavica
Berrin Oztas, Deniz Sahin, Hale Kir, Fatma Ceyla Eraldemir, Mert Musul, Sevinç Kuskay, Nurbay Ates
The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80μg/kg)+PTZ, and Group 5: NPY (60μg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained...
August 6, 2016: Neuropeptides
Tsugiko Kurita, Kotaro Sakurai, Youji Takeda, Toru Horinouchi, Ichiro Kusumi
OBJECTIVE: Surgical intervention can result in complete seizure remission rates of up to 80% in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). However, certain patients cannot be treated surgically for various reasons. We analyzed the very long-term clinical outcomes of patients with TLE-HS who could not be treated surgically. METHODS: Subjects were selected from among patients with TLE-HS who were actively followed up for >10 years and treated with medication without surgical treatment...
2016: PloS One
Reesha R Patel, Cindy Barbosa, Tatiana Brustovetsky, Nickolay Brustovetsky, Theodore R Cummins
Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels...
August 2016: Brain: a Journal of Neurology
Sakshi Piplani, Prabhakar Kumar Verma, Ajit Kumar
The unequivocal hypotheses about anticonvulsant activity of valproic acid (VPA) have always been a basic hurdle in designing next generation neurotherapeutics, particularly the anti-epileptic drugs. The present study reports about a comprehensive in-silico investigation into qualitative and quantitative binding of VPA and corresponding natural ligands of four major enzymes involved in neurotransmissions, namely-GABA transaminase (GABAt), α-keto glutarate dehydrogenase (α-KGDH), Succinate Semialdehyde dehydrogenase (SSADH) and Glutamate Decarboxylase (GAD), respectively...
July 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ming Ye, Yong-Feng Bi, Li Ding, Wei-Wei Zhu, Wei Gao
OBJECTIVE: Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure. METHODS: PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1β and TNF-α were then determined...
July 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Marieke H J van den Beuken-van Everdingen, Alexander de Graeff, Joost L M Jongen, Denise Dijkstra, Irina Mostovaya, Kris C Vissers
CONTEXT: In patients with cancer, pain is one of the most feared and burdensome symptoms. Adjuvant analgesics are an important cornerstone on which treatment of pain in patients with cancer is based. OBJECTIVES: To update our guidelines for the treatment of pain in patients with cancer, we performed a systematic review on the use of adjuvant analgesics in pain in cancer. METHODS: A systematic search of the literature was performed searching for articles that studied the effect of (1) antidepressants, (2) anti-epileptics, (3) N-methyl-d-aspartate (NMDA) receptor antagonists, and (4) other adjuvant analgesics in patients with cancer pain and described their effects on pain intensity and/or side effects...
May 21, 2016: Pain Practice: the Official Journal of World Institute of Pain
Shikha Kumari, Chandra Bhushan Mishra, Manisha Tiwari
Epilepsy is a complex neurological disorder which has plagued the human population through the ages and continues to affect about 50 million people worldwide. A better understanding of the pathogenesis of epilepsy unmasks various molecular targets for the treatment of epilepsy. The currently used antiepileptic drugs (AEDs) predominately target voltage-gated ion channels (Na+, Ca2+ and K+), GABAA receptor, glutamate receptor, synaptic vesicle 2A (SV2A) protein and carbonic anhydrase (CA). One group of AEDs acts on a single target while another group acts via multiple targets to control seizure episodes...
2016: Current Pharmaceutical Design
Ruhma Syeda, Jose S Santos, Mauricio Montal
KCNQ (voltage-gated K(+) channel family 7 (Kv7)) channels control cellular excitability and underlie the K(+) current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context...
February 5, 2016: Journal of Biological Chemistry
Tomoyuki Tanaka, Nana Yajima, Akihiko Tanitame, Tomoko Kiyoshi, Yoshiki Miura
In order to develop novel anti-epileptic drugs that are effective for both general and partial seizure, we conducted in vivo screening of our chemical library in the mice MES and sc-PTZ models and found the benzothiazine 1 as lead compound. Optimization of this compound led to the discovery of compound 7b, which showed potent anticonvulsant effect in the MES, scPTZ and rat amygdala kindling models. Since the chemical structure of 7b is different from that of any existing AED, it is suggested that 7b may have unique mechanism of action for relieving both partial and generalized epilepsy...
October 15, 2015: Bioorganic & Medicinal Chemistry Letters
Borna Payandemehr, Mahsima Khoshneviszadeh, Bardia Varastehmoradi, Ramtin Gholizadeh, Taraneh Bahremand, Hossein Attar, Arash Bahremand, Ahmad Reza Dehpour
Licofelone is a COX/5-LOX inhibitor, which recently was approved as an effective treatment for osteoarthritis. Beside its analgesic and anti-inflammatory effects, some reports show neuro-protective properties for this agent in central nervous system. Several lines of evidence declare the involvement of COX or LOX isoenzymes in epileptic disorders. To set the foundation for future research into the neurobiology of licofelone as a potential therapeutic agent, we studied the effect of licofelone in an animal model of epilepsy...
September 2015: Neurochemical Research
Bianca A Torres-Hernández, Lisa M Del Valle-Mojica, José G Ortíz
BACKGROUND: Anticonvulsant properties have been attributed to extracts of the herbal medicine Valeriana officinalis. Our aims were to examine the anticonvulsant properties of valerenic acid and valerian extracts and to determine whether valerian preparations interact with the activity of other anti-epileptic drugs (phenytoin or clonazepam). To achieve these goals, we validated the adult zebrafish, Danio rerio, as an animal model for studying anticonvulsant drugs. METHODS: All drug treatments were administered by immersion in water containing the drug...
2015: BMC Complementary and Alternative Medicine
Arun Kumar Sharma, Ekta Rani, Abdul Waheed, Satyendra K Rajput
Uncontrolled seizure or epilepsy is intricately related with an increase risk of pharmacoresistant epilepsy. The failure to achieve seizure control with the first or second drug trial of an anticonvulsant medication given at the appropriate daily dosage is termed as pharmacoresistance, despite the fact that these drugs possess different modes of action. It is one of the devastating neurological disorders act as major culprit of mortality in developed as well as developing countries with towering prevalence...
June 2015: Journal of Epilepsy Research
Bopanna I Kalappa, Heun Soh, Kevin M Duignan, Takeru Furuya, Scott Edwards, Anastasios V Tzingounis, Thanos Tzounopoulos
Voltage-gated Kv7 (KCNQ) channels are voltage-dependent potassium channels that are activated at resting membrane potentials and therefore provide a powerful brake on neuronal excitability. Genetic or experience-dependent reduction of KCNQ2/3 channel activity is linked with disorders that are characterized by neuronal hyperexcitability, such as epilepsy and tinnitus. Retigabine, a small molecule that activates KCNQ2-5 channels by shifting their voltage-dependent opening to more negative voltages, is an US Food and Drug Administration (FDA) approved anti-epileptic drug...
June 10, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Andrea Viggiano, Raffaele Pilla, Patrick Arnold, Marcellino Monda, Dominic D'Agostino, Giangennaro Coppola
The ketogenic diet is known to have an anti-epileptic effect; in fact it is currently used to treat drug resistant epilepsies. The efficacy of this diet is thought to be correlated to the elevation of blood ketone bodies. Because of problems with compliance to this diet, there is an interest in evaluating alternative pharmacological treatments that can have anti-seizure effects by elevating ketone bodies. In the present experiment, an orally administered synthetic ketone ester (R,S - 1,3-butanediol acetoacetate diester, or BD-AcAc2) was evaluated for its anti-seizure efficacy in a rat model...
August 27, 2015: Brain Research
Leila Moezi, Mahsa Hosseini, Simin Oveisi, Hossein Niknahad, Hamed Shafaroodi
Almost all antipsychotics have been associated with a risk of epileptic seizure provocation. Aripiprazole is a novel atypical antipsychotic. The risk of seizures with aripiprazole is reported to be the lowest among atypical agents. In this study, we investigated the effect of aripiprazole on seizure of mice in sub-chronic treatments. We also examined the interaction of nitric oxide (NO) with aripiprazole in seizure experiments. Mice received aripiprazole for 6 days and then on the 7th day aripiprazole was injected 60 min before intraperitoneal pentylenetetrazole or electroshock...
2015: Pharmacology
Sjors H W Schulpen, Jeroen L A Pennings, Aldert H Piersma
Differentiating pluripotent stem cells in vitro have proven useful for the study of developmental toxicity. Here, we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC)-based neurodevelopmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to noncytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), antiepileptic drugs known to cause neurodevelopmental toxicity. The effects observed on gene expression and correlated processes and pathways were in line with processes associated with neural development and pharmaceutical mode of action...
August 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
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