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G P Ivanova, L N Gorobets, A V Litvinov, V S Bulanov, L M Vasilenko
The review presents literature data reflecting the nature and mechanism of the effect of progesterone and its metabolites on human and animal brain structures. Particular attention is paid to neuroprotective, anticonvulsant, anti-anxiety and sedative properties of this hormone, which determines the prospect of its use for the prevention and treatment of human neurodegenerative diseases, epilepsy, sleep disorders, and anxiety-depressive spectrum disorders, including premenstrual and climacteric syndromes.
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Jingliang Zhang, Xiaoling Chen, Matti Kårbø, Yi Zhao, Long An, Rutao Wang, KeWei Wang, Zhuo Huang
Temporal lobe epilepsy (TLE), the most common pharmacoresistant focal epilepsy disorder, remains a major unmet medical need. Propofol is used as short-acting medication for general anesthesia and refractory status epilepticus with issues of decreased consciousness and memory loss. Dipropofol, a derivative of propofol, has been reported to exert antioxidative and antibacterial activities. Here we report that dipropofol exerted anticonvulsant activity in mouse model of kainic acid-induced seizures. Whole-cell patch clamp recordings of brain slices from the medial entorhinal cortex (mEC) revealed that dipropofol hyperpolarized the resting membrane potential and reduced the number of action potential firings, resulting in suppression of cortical neuronal excitability...
June 20, 2018: Journal of Neurophysiology
Anastasiya Nestsiarovich, Aurélien J Mazurie, Nathaniel G Hurwitz, Berit Kerner, Stuart J Nelson, Annette S Crisanti, Mauricio Tohen, Ronald L Krall, Douglas J Perkins, Christophe G Lambert
OBJECTIVES: This study compared 29 drugs for risk of psychiatric hospitalization in bipolar disorders, addressing the evidence gap on the >50 drugs used by US patients for treatment. METHODS: The Truven Health Analytics MarketScan® database was used to identify 190 894 individuals with bipolar or schizoaffective disorder who filled a prescription for one of 29 drugs of interest: lithium, first- or second-generation antipsychotics, mood-stabilizing anticonvulsants, and antidepressants...
June 19, 2018: Bipolar Disorders
Jarkko Kalliomäki, Bror Jonzon, Karin Huizar, Michael O'Malley, Anita Andersson, David M Simpson
Background and aims Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods This was a double-blind, randomized, parallel-group, multi-center study in patients with symmetric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years...
December 29, 2017: Scandinavian Journal of Pain
Marianne Rørbæk, Lise Ventzel, Hanne Gottrup
Background Neuropathic pain is usually treated with antidepressants and anticonvulsant. The use of systemic treatment is, however, limited due to poor tolerability and low efficacy. Qutenza, a topical capsaicin patch (8%), is a relatively new treatment for patients with peripheral neuropathic pain (PNP) conditions. The indication for using topical capsaicin treatment is peripheral neuropathic pain in patients without diabetes. Aim To describe the use of topical capsaicin treatment in a pain clinic in patients with PNP...
December 29, 2017: Scandinavian Journal of Pain
D Demant, K Lund, B Christensen, M Segerdahl, N Sjögren, T S Jensen, S Sindrup, N B Finnerup
Background In patients with neuropathic pain, Quantitative Sensory Testing (QST) can define different sensory phenotypes thought to be related to different underlying mechanisms. One phenotype with abnormal sensitization of cutaneous nociceptors has been termed irritable nociceptors. Methods This study is a part of a randomized, double-blind, placebo controlled, crossover trial with the anticonvulsant oxcarbazepine. The study is ongoing. In this report, baseline QST measures from patients with peripheral neuropathic pain due to either polyneuropathy (PNP) or peripheral nerve injury (PNI) are analyzed...
December 29, 2017: Scandinavian Journal of Pain
Villy Meineche-Schmidt, Niels-Henrik Jensen, Per Sjøgren
Background and aim The present study reports on chronic non-cancer patients who were referred to a private pain clinic, according to a waiting time guarantee and treated within one month from referral. Based on evaluation by members of the multidisciplinary staff at our pain clinic a pain management program could be offered individually or as group therapy. Methods Health related quality of life, psychometric tests, use of pain medication; socio-economic status and number of consultations in general practice were recorded at referral to the clinic and by postal questionnaires at follow-up 21 months later...
December 29, 2017: Scandinavian Journal of Pain
Karen Lund, Dyveke T Demant, Lene Vase, Søren H Sindrup, Troels S Jensen, Nanna B Finnerup
Background and aim Treatment responses during placebo periods in randomized clinical trials (RCTs) are quite often substantial and may impede a positive outcome of the trial. It would therefore be beneficial to gain more knowledge on factors contributing to large placebo responses in RCTs. The aim of the current study was to identify predictors of placebo responses in patients with peripheral neuropathic pain. Hypotheses We hypothesized that a high baseline pain intensity and variability will be predictive of large responses during placebo treatment...
December 29, 2017: Scandinavian Journal of Pain
Justine W Welsh, Valeria Tretyak, R Kathryn McHugh, Roger D Weiss, Olivera Bogunovic
BACKGROUND: Many patients require discontinuation of benzodiazepines due to a reduction in drug efficacy over time, the development of a sedative use disorder, or unwanted side effects. Benzodiazepine discontinuation can pose a significant challenge for prescribing clinicians due to potential withdrawal symptoms and a recurrence of psychiatric complaints. METHODS: A PubMed literature search was conducted using the medical subject heading of benzodiazepines in combination with the following key words: discontinuation, withdrawal, detoxification, cessation, dependence, addiction, substance use disorders, or long term...
May 31, 2018: Drug and Alcohol Dependence
Martin W Nicholson, Aaron Sweeney, Eva Pekle, Sabina Alam, Afia B Ali, Michael Duchen, Jasmina N Jovanovic
Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABAA Rs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised...
June 14, 2018: Molecular Psychiatry
Li-Wen Chen, Chao-Ku Teng, Yi-Shan Tsai, Jieh-Neng Wang, Yi-Fang Tu, Ching-Fen Shen, Ching-Chuan Liu
INTRODUCTION: Seasonal influenza-associated neurological complications had high mortality and morbidity rates in recent studies. We reported influenza-associated encephalitis/encephalopathy in children during 2014-2017 in Taiwan, focusing on neurological presentations, neuroimaging correlations, and critical care managements. MATERIALS/SUBJECTS: During January 1st 2014 to June 30th 2017, pediatric patients reported to the Taiwan Centers for Disease Control surveillance system for severe complicated influenza infections in the hospital were retrospectively reviewed...
June 8, 2018: Brain & Development
Pricila Pfluger, Vanessa Rodrigues Coelho, Gabriela Gregory Regner, Lucas Lima da Silva, Karina Martinez, Alan Fonseca, Cassiana Macagnan Viau, Patricia Pereira
BACKGROUND: Gamma-decanolactone (GD) is a monoterpene compound that presents anticonvulsant effect in acute and chronic models of epilepsy and it acts as a noncompetitive glutamate antagonist. OBJECTIVE: This study evaluated the anticonvulsant profile and the possible mechanism of action of GD in seizures induced by isoniazid (INH; 250 mg/kg), picrotoxin (PCT; 5 mg/kg) and 4-aminopyridine (4-AP; 13 mg/kg) in male mice. METHOD: Thirty minutes before the convulsants administration, animals received a single administration of saline, GD (100 or 300 mg/kg) or the positive control diazepam (DZP; 2 mg/kg)...
June 10, 2018: Central Nervous System Agents in Medicinal Chemistry
Shiwei Song, Abul Fajol, Yan Chen, Baogang Ren, Songsheng Shi
Epilepsy is associated with increased morbidity and mortality together and places a large financial burden on individuals and society. To evaluate the anticonvulsant action of protodioscin (PDSN) in experiments with animals with pilocarpine-induced convulsions. We assessed the activity of PDSN in pilocarpine induced seizures in combination with different agents which are acting via diverse receptors, such as atropine, memantine, nimodipine, diazepam, and flumazenil, to determine the exact receptors responsible for the action of PDSN...
June 7, 2018: European Journal of Pharmacology
Yunli Liu, Baohua Hou, Yusong Zhang, Yuanteng Fan, Biwen Peng, Wanhong Liu, Song Han, Jun Yin, Xiaohua He
Epilepsy is a common neurological disorder with a complex etiology. Our previous study demonstrated that dipeptidyl peptidase IV (DPP4) may be associated with the pathogenesis of epilepsy. However, whether the DPP4 inhibitor sitagliptin has an anticonvulsant effect and the underlying mechanism remain to be elucidated. In this study, we determined that sitagliptin remarkably attenuated the severity of seizures in a pentylenetetrazole (PTZ)-induced rat model. In addition, sitagliptin decreased epileptiform activity measured by electroencephalography (EEG) recordings and patch-clamp methods...
June 6, 2018: Experimental Neurology
Chandra Bhushan Mishra, Shikha Kumari, Fouzia Siraj, Rajesh Yadav, Sweta Kumari, Ankit Kumar Tiwari, Manisha Tiwari
Epilepsy is a chronic neurological disorder which affects 65 million worldwide population and characterized by recurrent seizure in epileptic patients. Recently, we reported a novel piperonylpiperazine derivative, BPPU "1-[4-(4-benzo [1,3]dioxol-5-ylmethyl-piperazin-1-yl)- phenyl]-3-phenyl-urea'' as a potent anticonvulsant agent. BPPU has shown excellent anticonvulsant activity in various in-vivo seizure models along with good anti-depressant activity. In this report, we have deeply examined the anti-epileptogenic potential of BPPU in pentylenetetrazole (PTZ) induced kindling model and BPPU effectively reduced seizure episodes in kindled animals upto 35 days...
June 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Salia Farrokh, Pouya Tahsili-Fahadan, Eva K Ritzl, John J Lewin, Marek A Mirski
BACKGROUND: The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity...
June 7, 2018: Critical Care: the Official Journal of the Critical Care Forum
Marine Movsisyan, Thomas Heugebaert, Bart Roman, Rudy Dams, Rudy Van Campenhout, Matthias Conradi, Chris Victor Stevens
3-Chloropropionyl chloride is a chemically versatile building block with applications in the field of adhesives, pharmaceuticals, herbicides and fungicides. Its current production entails problems concerning safety, prolonged reaction times and the use of excessive amounts of chlorinating reagents. We developed a continuous flow procedure for acid chloride formation from acrylic acid and a consecutive 1,4-addition of hydrogen chloride generating 3-chloropropionyl chloride, as presented in this paper. Up to 94% conversion was reached in 25 minutes at mild temperatures and pressures...
June 7, 2018: Chemistry: a European Journal
L F D van Vulpen, K Holstein, C Martinoli
Haemarthroses cause major morbidity in patients with haemophilia. Blood has devastating effects on all joint components, resulting in synovitis, osteochondral degeneration and ultimately end-stage haemophilic arthropathy. Key players in this process are iron and inflammation. Preventing joint bleeds is of utmost importance to maintain joint health as targeted therapies directed against blood-induced inflammation and iron-mediated processes are lacking. Joint bleeds result in acute pain as well as chronic pain due to synovitis or arthropathy...
May 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Juan Salvatierra, Joel Castro, Andelain Erickson, Qian Li, Joao Braz, John Gilchrist, Luke Grundy, Grigori Y Rychkov, Annemie Deiteren, Rana Rais, Glenn F King, Barbara S Slusher, Allan Basbaum, Pankaj J Pasricha, Stuart M Brierley, Frank Bosmans
Functional bowel disorder patients can suffer from chronic abdominal pain, likely due to visceral hypersensitivity to mechanical stimuli. As there is only a limited understanding of the basis of chronic visceral hypersensitivity (CVH), drug-based management strategies are ill defined, vary considerably, and include NSAIDs, opioids, and even anticonvulsants. We previously reported that the 1.1 subtype of the voltage-gated sodium (NaV; NaV1.1) channel family regulates the excitability of sensory nerve fibers that transmit a mechanical pain message to the spinal cord...
June 7, 2018: JCI Insight
Yonas Raru, Fuad Zeid
Valproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric symptoms, including bipolar disorder, borderline personality disorder, and alcohol withdrawal. Valproate is associated with severe idiosyncratic adverse effects, the most notable being valproate-induced hyperammonemic encephalopathy (VHE). Topiramate is also a broad-spectrum anticonvulsant that is also extensively used for migraine prophylaxis, as a mood stabilizer, and for alcohol dependency. There is increased occurrence of VHE when valproate is used with other medications like phenytoin, phenobarbital, and topiramate...
2018: Respiratory Medicine Case Reports
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