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https://www.readbyqxmd.com/read/29778948/bioisosteres-of-ethyl-8-ethynyl-6-pyridin-2-yl-4h-benzo-f-imidazo-1-5-a-1-4-diazepine-3-carboxylate-hz-166-as-novel-alpha-2-3-selective-potentiators-of-gaba-a-receptors-improved-bioavailability-enhances-anticonvulsant-efficacy
#1
J M Witkin, J L Smith, X Ping, S D Gleason, M M Poe, G Li, X Jin, J Hobbs, J M Schkeryantz, J S McDermott, A I Alatorre, J N Siemian, J W Cramer, D C Airey, K R Methuku, V V N P B Tiruveedhula, T M Jones, J Crawford, M J Krambis, J L Fisher, J M Cook, R Cerne
HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778946/mechanisms-underlying-anticonvulsant-and-proconvulsant-actions-of-norepinephrine
#2
REVIEW
Maedeh Ghasemi, Nasrin Mehranfard
Norepinephrine (NE) has been shown to exert a potent suppressant effect on seizure development. On the other hand, several lines of evidence have shown that increased NE level is proconvulsant under certain conditions. These data suggest that variations in NE levels could affect modulatory action of noradrenergic system on seizures. Less, however, is known about the mechanisms by which adrenergic pathways protect against seizures or promote seizures. Knowing the mechanisms involved in anti- or proconvulsive effects of NE may help to the development of new therapeutic candidates for patients with refractory epilepsy...
May 11, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29777444/comparison-of-lawsone-contents-among-lawsonia-inermis-plant-parts-and-neurite-outgrowth-accelerators-from-branches
#3
Yoshimi Oda, Souichi Nakashima, Erina Kondo, Seikou Nakamura, Mamiko Yano, Chisa Kubota, Yusuke Masumoto, Minami Hirao, Yuki Ogawa, Hisashi Matsuda
Lawsonia inermis L. (Lythraceae) is cultivated in many countries, including Japan, China, India and Egypt. Its leaves are well known as hair dye and exhibit antibacterial, anticancer, antifungal and anticonvulsant activities. However, there are few reports on its branches. 2-Hydroxy-1,4-naphthoquinone (lawsone) is a characteristic compound in its leaves. However, it remains to be clarified whether lawsone is present in other plant parts or not. In this study, we measured lawsone contents in the extracts of L...
May 17, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29776417/sinomenine-exerts-anticonvulsant-profile-and-neuroprotective-activity-in-pentylenetetrazole-kindled-rats-involvement-of-inhibition-of-nlrp1-inflammasome
#4
Bo Gao, Yu Wu, Yuan-Jian Yang, Wei-Zu Li, Kun Dong, Jun Zhou, Yan-Yan Yin, Da-Ke Huang, Wen-Ning Wu
BACKGROUND: Epilepsy is a common neurological disorder and is not well controlled by available antiepileptic drugs (AEDs). Inflammation is considered to be a critical factor in the pathophysiology of epilepsy. Sinomenine (SN), a bioactive alkaloid with anti-inflammatory effect, exerts neuroprotective activity in many nervous system diseases. However, little is known about the effect of SN on epilepsy. METHODS: The chronic epilepsy model was established by pentylenetetrazole (PTZ) kindling...
May 18, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29774497/safety-of-commercial-airflight-in-patients-with-brain-tumors-a-case-series
#5
Michelle Phillips, Marlon Saria, Amy Eisenberg, Daniel F Kelly, Garni Barkhoudarian
INTRODUCTION: Patients with intracranial masses are often advised to avoid airflight due to concerns of worsening neurological symptoms or deterioration. However, many patients often travel cross-country or internationally to tertiary care centers for definitive care. This study assesses the safety of commercial airflight for brain and skull base tumor patients without severe or progressive neurological deficits. METHODS: Patients that had traveled to our institution for surgery via commercial airflight from 2014 to 2017 were identified...
May 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29772556/perinatal-brain-injury-mechanisms-and-therapeutic-approaches
#6
Joanne O Davidson, Justin M Dean, Mhoyra Fraser, Guido Wassink, Ted C Andelius, Simerdeep K Dhillon, Laura Bennet, Alistair Jan Gunn
Brain damage resulting from perinatal hypoxia-ischemia evolves slowly over time. While a small number of brain cells may die during a sufficiently profound period of hypoxia-ischemia, many will show initial recovery during a "latent" phase characterized by actively suppressed neural metabolism and activity. Critically, this transient recovery may be followed after ~6 hours by a phase of secondary deterioration, with delayed seizures, failure of mitochondrial function, cytotoxic edema, and bulk cell death over ~72 hours...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770251/review-of-the-neurological-benefits-of-phytocannabinoids
#7
REVIEW
Joseph Maroon, Jeff Bost
Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS...
2018: Surgical Neurology International
https://www.readbyqxmd.com/read/29769109/valproate-induced-hyperammonemia-uncovering-an-underlying-inherited-metabolic-disorder-a-case-report
#8
Shaine Mehta, Sarrah Tayabali, Robin Lachmann
BACKGROUND: Sodium valproate is a commonly used anticonvulsant. It is widely recognized that valproate can cause hyperammonemia, particularly in people with underlying liver disease. Patients with urea cycle disorders are genetically predisposed to this adverse event and can develop severe hyperammonemia if given valproate. This can occur even if liver functions tests and plasma concentration of valproate are normal, highlighting the importance of checking ammonia levels in any patient presenting with encephalopathy...
May 17, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29766827/pain-related-behavior-and-brain-activation-in-a-cynomolgus-macaque-model-of-postoperative-pain
#9
Aldric Hama, Takahiro Natsume, Shin'ya Ogawa, Yūji Awaga, Ikuo Hayashi, Akihisa Matsuda, Hiroyuki Takamatsu
BACKGROUND: Inadequate postoperative pain management could lead to persistent pain and this is, in part, due to incomplete understanding of the mechanism of postoperative pain. Currently available rodent models may have limited translatability to clinical postoperative pain. Thus, a preclinical model of postoperative pain was developed in the cynomolgus macaque, a species that is phylogenetically closer to humans than rodents. METHOD: The presence of pressure hypersensitivity was assessed with non-noxious pressure applied proximally and distally (approximately 10 cm) to an abdominal incision in macaques...
May 15, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29766822/2-5-disubstituted-phthalimides-design-synthesis-and-anticonvulsant-activity-in-scptz-and-mes-models
#10
Atefeh Saadabadi, Babak Kohen, Maryam Irandoust, Hamed Shafaroudi, Tara Mohammadpour, Mahdi Rezayat, Asghar Davood
In this study, fifteenth new 2,5-disubstituted analgouges of phthalimide were designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) compare to phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FT-IR, H-NMR, C-NMR and MASS spectroscopy. All the tested compounds were found to be effective in the PTZ model at the dose of 60 mg/kg and most of the compounds showed protection against MES test indicative of their ability to inhibit the seizure spread at the all dose ranges...
May 15, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29766538/chronic-exposure-to-cannabidiol-induces-reproductive-toxicity-in-male-swiss-mice
#11
Renata K Carvalho, Monaliza L Santos, Maingredy R Souza, Thiago L Rocha, Francisco S Guimarães, Janete A Anselmo-Franci, Renata Mazaro-Costa
Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. CBD was orally administered to 21-day-old male Swiss mice at doses of 15 and 30 mg kg-1 daily (CBD 15 and 30 groups, respectively), with a control group receiving sunflower oil, for 34 consecutive days...
May 16, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29765245/the-epidemiology-of-outpatient-pain-treatment-in-pediatrics
#12
Stacy Baldridge, Laura Wallace, Aditi Kadakia
Background: There is limited real-world, population-level data on the prevalence and treatment of pain in children. An understanding of pediatric pain conditions and its management can help inform provider education, treatment guidelines, and design of pediatric pain studies. Therefore, in this study, we aimed to describe the prevalence of conditions associated with acute and chronic pain in pediatric patients and to characterize pediatric pain treatment with nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 (COX-2) inhibitors, opioids (immediate release or extended release), antidepressants, topical analgesics, anticonvulsants, and other therapies based on a large, real-world sample...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29761125/inflammation-is-a-key-risk-factor-for-persistent-seizures-in-neurocysticercosis
#13
Jesica A Herrick, Biswajit Maharathi, Jin Suh Kim, Gerardo G Abundis, Anjali Garg, Isidro Gonzales, Herbert Saavedra, Javier A Bustos, Hector H Garcia, Jeffrey A Loeb
Objective: We conducted a retrospective, case-control study of neurocysticercosis patients to ascertain early markers that identify subjects likely to develop treatment-resistant seizures. Methods: Clinical histories and imaging studies from 38 neurocysticercosis patients who had been followed for 18 months after treatment were evaluated. Both pairwise and multifactorial analyses were conducted to identify factors associated with continued seizures. Results: Eleven of 38 patients continued to have seizures during the follow-up period...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29758584/inhibition-of-sympathetic-sprouting-in-ccd-rats-by-lacosamide
#14
Yuying Wang, Fuquan Huo
BACKGROUND: Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG). Since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. METHODS: LCM (50 mg/kg) was daily injected intraperitoneally into rats subjected to chronic compression DRG (CCD), an animal model of neuropathic pain that exhibits sympathetic nerve sprouting, for the 1st 7 days after injury...
May 14, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29756718/-drug-reaction-with-eosinophilia-and-systemic-symptoms-due-to-carbamazepine-pediatric-case
#15
Rocío Del P Pereira-Ospina, Ana M Bejarano-Quintero, José M Suescún-Vargas, Javier Y Pinzón-Salamanca
Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000- 10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine...
June 1, 2018: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/29754132/recovery-of-brain-abscess-induced-stuttering-after-neurosurgical-intervention
#16
Daisuke Sudo, Youichi Doutake, Hidenori Yokota, Eiju Watanabe
Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess. The patient was a 60-year-old man admitted for a seizure and administered an anticonvulsant, after which he began stuttering. MRI revealed a brain abscess in the left frontal lobe that extended to the dorsolateral prefrontal cortex (BA (Brodmann's area) 9 and 46), frontal eye field (BA 8) and premotor cortex and supplementary motor area (BA 6)...
May 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29754108/knowledge-of-women-issues-and-epilepsy-among-doctors-in-sudan
#17
Awab K Elnaeim, Mohamed K Elnaeim, Ismat B A Babiker
OBJECTIVE: The objective of this study was to assess the knowledge of doctors in Sudan about women issues related to epilepsy. METHODS: In this cross-sectional study that was conducted in Sudan during the period from October 2017 to December 2017, we used Google forms to collect data from 154 doctors using Knowledge of Women Issues and Epilepsy (KOWIE) II standardized questionnaire. RESULTS: Our studied group included house officers (n = 34), medical officers (n = 60), registrars (n = 52), and specialists (n = 8)...
May 10, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29753923/prevalence-of-valproate-syndrome-in-europe-from-2005-to-2014-a-registry-based-multi-centre-study
#18
Joan K Morris, Ester Garne, Maria Loane, Marie-Claude Addor, Ingeborg Barisic, Fabrizio Bianchi, Miriam Gatt, Monica Lanzoni, Catherine Lynch, Olatz Mokoroa, Vera Nelen, Amanda Neville, Mary T O'Mahony, Hanitra Randrianaivo-Ranjatoelina, Anke Rissmann, David Tucker, H E K de Walle, Nataliia Zymak-Zakutnia, Judith Ankin
Women with epilepsy need to continue to take anticonvulsants during their pregnancies to prevent seizures from occurring. Since the 1980's, it has been known that the use of valproate (an anticonvulsant) in the first trimester of pregnancy is associated with an increased risk of spina bifida. Recent studies have also demonstrated increased risks of other congenital anomalies as well as a risk of cognitive impairment. Doctors in the EU are now advised not to prescribe valproate in pregnant women, in women who can become pregnant or in girls unless other treatments are ineffective or not tolerated...
May 10, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29753867/topiramate-mitigates-3-nitropropionic-acid-induced-striatal-neurotoxicity-via-modulation-of-ampa-receptors
#19
Heba N Shalaby, Dalia M El-Tanbouly, Hala F Zaki
Prevalence of glutamate receptor subunit 2 (GluR2)-lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is a hallmark of excitotoxicity-related neurodegenerative diseases. Topiramate (TPM) is a structurally novel anticonvulsant with a well-known modulatory effects on AMPA/kainate subtypes of glutamate receptors. The present study aimed at investigating the neuroprotective potential of TPM on 3-nitropropionic acid (3-NP)-induced striatal neurodegeneration and Huntington's disease-like symptoms...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29751140/nanoparticle-based-delivery-of-carbamazepine-a-promising-approach-for-the-treatment-of-refractory-epilepsy
#20
Anna Zybina, Anastasiya Anshakova, Julia Malinovskaya, Pavel Melnikov, Vladimir Baklaushev, Vladimir Chekhonin, Olga Maksimenko, Sergey Titov, Vadim Balabanyan, Jörg Kreuter, Svetlana Gelperina, Kenul Abbasova
Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy...
May 8, 2018: International Journal of Pharmaceutics
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