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Drug induced lower seizure potential

Bassem Sadek, Ali Saad, Gniewomir Latacz, Kamil Kuder, Agnieszka Olejarz, Tadeusz Karcz, Holger Stark, Katarzyna Kieć-Kononowicz
A series of twelve novel non-imidazole-based ligands (3-14) was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R). The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3-14) tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES)-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally), whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ) model...
2016: Drug Design, Development and Therapy
Bogdan Pintea, Kevin Hampel, Jan Boström, Rainer Surges, Hartmut Vatter, Ilana S Lendvai, Thomas M Kinfe
OBJECTIVES: Invasive vagal nerve stimulation (iVNS) is an established treatment option for drug-resistant focal seizures and has been assumed to diminish frequent co-incidental daily headache/migraine. However, long-term effects on cognitive/affective head pain perception, headache intensity/frequency are lacking. We therefore investigated potential iVNS-induced effects in patients with drug-resistant focal seizure and daily headache/migraine. MATERIALS AND METHODS: A clinical database was used to select 325 patients with drug-resistant epilepsy treated by either iVNS plus best medical treatment (BMT) or BMT alone, compared to a healthy control group (HC)...
November 22, 2016: Neuromodulation: Journal of the International Neuromodulation Society
Tian-Hui Wu, Fei Yin, Jing Peng, Hui-Min Kong, Lin-Hong Li
OBJECTIVE: To study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats. METHODS: Forty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma
Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i...
November 2016: Neuropharmacology
Nandhakumar Balakrishnan, Marna Ericson, Ricardo Maggi, Edward B Breitschwerdt
BACKGROUND: The genus Bartonella is comprised of a rapidly increasing number of pathogenic species that induce a seemingly diverse spectrum of neurological symptoms. During the 12 year period that followed the initial onset of neurological and gastrointestinal symptoms, an 11 year-old girl experienced a spectrum of neurological complaints including frequent headaches, visual and auditory hallucinations, anxiety, vision loss involving the lower left quadrant of both eyes, episodic bouts of generalized paralysis, facial palsy, chronic insomnia, seizures, dizziness, cognitive dysfunction, and memory loss...
May 10, 2016: Parasites & Vectors
Erwin A van Vliet, Willem M Otte, Wytse J Wadman, Eleonora Aronica, Gijs Kooij, Helga E de Vries, Rick M Dijkhuizen, Jan A Gorter
OBJECTIVE: The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis. METHODS: Imaging was repeatedly performed until 6 weeks after kainic acid-induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle-treated rats, using gadobutrol as contrast agent...
January 2016: Epilepsia
Christine E Dobek, Daniel M Blumberger, Jonathan Downar, Zafiris J Daskalakis, Fidel Vila-Rodriguez
OBJECTIVE: When considering repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder, clinicians often face a lack of detailed information on potential interactions between rTMS and pharmacotherapy. This is particularly relevant to patients receiving bupropion, a commonly prescribed antidepressant with lower risk of sexual side effects or weight increase, which has been associated with increased risk of seizure in particular populations. Our aim was to systematically review the information on seizures occurred with rTMS to identify the potential risk factors with attention to concurrent medications, particularly bupropion...
2015: Neuropsychiatric Disease and Treatment
Minho Hong, Ki Duk Song, Hak-Kyo Lee, SunShin Yi, Yong Seok Lee, Tae-Hwe Heo, Hyun Sik Jun, Sung-Jo Kim
Batten disease (BD; also known as juvenile neuronal ceroid lipofuscinosis) is a genetic disorder inherited as an autosomal recessive trait and is characterized by blindness, seizures, cognitive decline, and early death resulting from the inherited mutation of the CLN3 gene. Mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, disrupted autophagy, and enhanced apoptosis have been suggested to play a role in BD pathogenesis. Fibrates, a class of lipid-lowering drugs that induce peroxisome proliferator-activated receptor-α (PPAR-α) activation, are the most commonly used PPAR agonists...
March 2016: In Vitro Cellular & Developmental Biology. Animal
Tracy Glauser, Antonio Laurenza, Haichen Yang, Betsy Williams, Tony Ma, Randi Fain
Perampanel is a selective, noncompetitive AMPA receptor antagonist with demonstrated efficacy and tolerability in partial seizures in patients aged ≥ 12 years in Phase III studies. Post-hoc analysis of these studies was conducted to determine the efficacy and tolerability of perampanel based on the number of concomitant antiepileptic drugs (AEDs) at baseline, as well as to examine which baseline characteristics, if any, were predictors of efficacy. Efficacy parameters were based on the number of baseline AEDs, and logistic regression analyses were used to evaluate the association of demographic and baseline clinical factors with probability of ≥ 50% reduction in seizure frequency...
January 2016: Epilepsy Research
Lin Yu, Xu Ke-Ke, Chen Chao-Yong, Zhang Rui-Tong, Lan Ming, Li Shao-Hua, Pan Ling-Zhen, Zhang Tian-E, Yan Zhi-Yong
BACKGROUND: Recently we found the ethanolic extract and iridoid-rich fraction from Valeriana jatamansi Jones, which is a traditional Chinese medicine exhibited anxiolytic properties. OBJECTIVE: This study aims to the substance dependence effect of the ethanolic extract and iridoid-rich fraction. MATERIALS AND METHODS: The study included two experiments: Mice were given orally with ethanolic extract for 12 weeks or iridoid-rich fraction for 16 weeks in experiment I and experiment II, respectively...
October 2015: Pharmacognosy Magazine
Dan Kaufmann, Emily A Bates, Boris Yagen, Meir Bialer, Gerald H Saunders, Karen Wilcox, H Steve White, K C Brennan
BACKGROUND: Though migraine is disabling and affects 12%-15% of the population, there are few drugs that have been developed specifically for migraine prevention. Valproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that is also used for migraine prophylaxis, but its clinical use is limited by its side effect profile. sec-Butylpropylacetamide (SPD) is a novel VPA derivative, designed to be more potent and tolerable than VPA, that has shown efficacy in animal seizure and pain models...
September 2016: Cephalalgia: An International Journal of Headache
Anna N Vongerichten, Gustavo Sato dos Santos, Kirill Aristovich, James Avery, Andrew McEvoy, Matthew Walker, David S Holder
Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex...
January 1, 2016: NeuroImage
Jiana Shi, Huimin Xu
A 73-year-old female patient developed a generalized tonic-clonic seizure on the 6th day after treatment with moxifloxacin 400 mg daily intravenously for appendicitis. This patient had atrial fibrillation and history of a surgery for intracerebral hemorrhage, with impaired renal function and liver function, but without history of seizures. Moxifloxacin was discontinued and switched to cefuroxime. The patient remained seizure-free at discharge four days later. The naranjo adverse drug reaction probability scale score was 4, indicating a possible adverse reaction to moxifloxacin...
September 2014: Iranian Journal of Public Health
Siddesh Besur, Paul Schmeltzer, Herbert L Bonkovsky
BACKGROUND: Porphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP). DISCUSSION: AIP is the most common, and ALADP is the least common acute porphyria...
September 2015: Journal of Emergency Medicine
R Davis, M I Wilde
SYNOPSIS: Mirtazapine is a tetracyclic antidepressant with a novel mechanism of action; it increases noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors. The increased release of serotonin (5-hydroxytryptamine; 5-HT) stimulates serotonin 5-HT1 receptors because mirtazapine directly blocks 5-HT2 and 5-HT3 receptors. The enhancement of both noradrenergic- and 5-HT1 receptor-mediated neurotransmission is thought to be responsible for the antidepressant activity of mirtazapine...
May 1996: CNS Drugs
Sasan Zaeri, Masoumeh Emamghoreishi
BACKGROUND: N-acetylcysteine (NAC) has been indicated against experimental seizures, but with relatively inconclusive results. This study was undertaken to evaluate whether NAC exerts a dose-dependent anticonvulsant effect and to determine NAC safe therapeutic dose range and its muscle-relaxant activity in both acute and chronic uses. METHODS: Following intraperitoneal (i.p.) administration of N-acetylcysteine acutely (50-300 mg/kg) or chronically for 8 days (25-300 mg/kg), mice were injected with PTZ (90 mg/kg, i...
March 2015: Iranian Journal of Medical Sciences
Ze-Jun Wang, Liqin Sun, Thomas Heinbockel
Cinobufagin and resibufogenin are two major effective bufadienolides of Chan su (toad venom), which is a Chinese medicine obtained from the skin venom gland of toads and is used as a cardiotonic and central nervous system (CNS) respiratory agent, an analgesic and anesthetic, and as a remedy for ulcers. Many clinical cases showed that Chan su has severe side-effects on the CNS, causing shortness of breath, breathlessness, seizure, coma and cardiac arrhythmia. We used whole-cell recordings from brain slices to determine the effects of bufadienolides on excitability of a principal neuron in main olfactory bulb (MOB), mitral cells (MCs), and the cellular mechanism underlying the excitation...
2014: PloS One
Se Jin Kim, Byung Woo Jhun, Ji Eun Lee, Kang Kim, Hyeun Yong Choi
Valproic acid is one of the most common antiepileptic drugs used for the treatment of several seizure disorders. A 20-year-old man presented with a sudden decline of consciousness. He had a neurosurgery operation for intracranial and intraventricular hemorrhage. Following surgery, antiepileptic medication was administered to the patient in order to control his seizure events. On valproic acid treatment, he began to complain of fever and dyspnea. His symptoms persisted despite receiving empirical antibiotic treatment...
September 2014: Tuberculosis and Respiratory Diseases
Yohei Fujimoto, Tomoharu Funao, Koichi Suehiro, Ryota Takahashi, Takashi Mori, Kiyonobu Nishikawa
BACKGROUND: Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. METHODS: Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan...
January 2015: Anesthesiology
Kavita Gulati, Arunabha Ray
Nitric oxide is a simple, ubiquitous, diatomic molecule with complex neuromodulatory functions. Anxiety and seizures are closely similar neurobehavioral disorders and are regulated by limbic system. The present study evaluated the regulatory roles of NO in these pathophysiological states in experimental models. In test for anxiety, aminophylline induced anxiogenic responses were assessed by the elevated plus maze (EPM) test, and a low dose of the drug (50 mg/kg) reduced both open arm entries and open arm time in rats...
December 1, 2014: Nitric Oxide: Biology and Chemistry
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