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Eslicarbazepine Acetate: a New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures
Drugs R D DOI 10.1007/s40268-017-0197-5 REVIEW ARTICLE Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures 1 1 1 Graciana L. Galiana • Angela C. Gauthier • Richard H. Mattson Ó The Author(s) 2017. This article is an open access publication Abstract Eslicarbazepine acetate is a new anti-epileptic drug belonging to the dibenzazepine carboxamide family Key Points that is currently approved as adjunctive therapy and monotherapy for partial-onset (focal) seizures. The drug Eslicarbazepine acetate is an effective and safe enhances slow inactivation of voltage-gated sodium chan- treatment option for partial-onset seizures as nels and subsequently reduces the activity of rapidly firing adjunctive therapy and monotherapy. neurons. Eslicarbazepine acetate has few, but some, drug– drug interactions. It is a weak enzyme inducer and it Eslicarbazepine acetate improves upon its inhibits cytochrome P450 2C19, but it affects a smaller predecessors, carbamazepine and oxcarbazepine, by assortment of enzymes than carbamazepine. Clinical being available in a once-daily regimen, interacting studies using eslicarbazepine acetate as adjunctive treat- with a smaller range of drugs, and causing less side ment or monotherapy have demonstrated its efficacy in effects. patients with refractory or newly diagnosed focal seizures. The drug is generally well tolerated, and the most common side effects include dizziness, headache, and diplopia. One of the greatest strengths of eslicarbazepine acetate is its ability to be administered only once per day. Eslicar- 1 Introduction bazepine acetate has many advantages over older anti- epileptic drugs, and it should be strongly considered when Epilepsy is a common neurological disorder affecting over treating patients with partial-onset epilepsy. -
(12) Patent Application Publication (10) Pub. No.: US 2015/0025060A1 Tamarkin Et Al
US 2015.0025060A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0025060A1 Tamarkin et al. (43) Pub. Date: Jan. 22, 2015 (54) FOAMABLE COMPOSITIONS AND KITS (30) Foreign Application Priority Data COMPRISING ONE ORMORE OF A CHANNEL AGENT, ACHOLINERGICAGENT, Oct. 25, 2002 (IL) .......................................... 1524.86 A NITRC OXDE DONOR AND RELATED AGENTS AND THEIR USES Publication Classification (71) Applicant: Foamix Pharmaceuticals Ltd., Rehovot (51) Int. Cl. (IL) A613 L/554 (2006.01) A 6LX3 L/505 (2006.01) (72) Inventors: Dov Tamarkin, Macabim (IL); Meir A647/10 (2006.01) Eini, Ness Ziona (IL); Doron Friedman, A613 L/4422 (2006.01) Karmei Yosef (IL); Tal Berman, Rishon (52) U.S. Cl. Le Ziyyon (IL); Alex Besonov, Rehovot CPC ........... A6 IK3I/554 (2013.01); A61 K3I/4422 (IL) (2013.01); A61 K3I/505 (2013.01); A61 K 47/10 (2013.01) (21) Appl. No.: 14/448,670 USPC ....................... 514/211.03: 514/356; 514/275 (22) Filed: Jul. 31, 2014 (57) ABSTRACT Related U.S. Application Data The present invention relates to a foamable therapeutic com position comprising: (a) a therapeutically effective concen (63) Continuation of application No. 1 1/767,442, filed on tration of at least one active agent selected from the group Jun. 22, 2007, which is a continuation-in-part of appli consisting of a channel agent, a cholinergic agent, and a nitric cation No. 10/911.367, filed on Aug. 4, 2004, said oxide donor; and (b) a foamable carrier comprising: application No. 1 1/767,442 is a continuation-in-part of i. -
Chapter 25 Mechanisms of Action of Antiepileptic Drugs
Chapter 25 Mechanisms of action of antiepileptic drugs GRAEME J. SILLS Department of Molecular and Clinical Pharmacology, University of Liverpool _________________________________________________________________________ Introduction The serendipitous discovery of the anticonvulsant properties of phenobarbital in 1912 marked the foundation of the modern pharmacotherapy of epilepsy. The subsequent 70 years saw the introduction of phenytoin, ethosuximide, carbamazepine, sodium valproate and a range of benzodiazepines. Collectively, these compounds have come to be regarded as the ‘established’ antiepileptic drugs (AEDs). A concerted period of development of drugs for epilepsy throughout the 1980s and 1990s has resulted (to date) in 16 new agents being licensed as add-on treatment for difficult-to-control adult and/or paediatric epilepsy, with some becoming available as monotherapy for newly diagnosed patients. Together, these have become known as the ‘modern’ AEDs. Throughout this period of unprecedented drug development, there have also been considerable advances in our understanding of how antiepileptic agents exert their effects at the cellular level. AEDs are neither preventive nor curative and are employed solely as a means of controlling symptoms (i.e. suppression of seizures). Recurrent seizure activity is the manifestation of an intermittent and excessive hyperexcitability of the nervous system and, while the pharmacological minutiae of currently marketed AEDs remain to be completely unravelled, these agents essentially redress the balance between neuronal excitation and inhibition. Three major classes of mechanism are recognised: modulation of voltage-gated ion channels; enhancement of gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission; and attenuation of glutamate-mediated excitatory neurotransmission. The principal pharmacological targets of currently available AEDs are highlighted in Table 1 and discussed further below. -
Analysis of Pregabalin and Lacosamide Using the Post-Marketing Antiepileptic Drug/Device Survey
Analysis of Pregabalin and Lacosamide Using the Post-Marketing Antiepileptic Drug/Device Survey. Analyse de la prégabaline et lacosamide utilisant l’enquête post marketing médicament appareil antiépileptique. Jeorge L. Morris , Johnson, EPb Aurora Epilepsy Center, Aurora St Luke’s Medical Center, (USA) University of Wisconsin Milwaukee, Milwaukee, WI Email: [email protected] No disclosure to be declared. Résumé also expanded the population eligible to receive drug Les patients atteints de l’épilepsie ont bénéficié d’un certain treatment. This expansion of the treatable population to nombre de nouveaux médicaments dans le traitement special groups such as the elderly, pregnant women and des crises partielles. En plus d’être de nouvelles options children has caused doctors to make choices between de traitement, ces médicaments ont également élargi the available medications based on perceptions of safety. la population cibles de ces traitements médicamenteux. Some key information that could guide a physician’s choice Cette expansion de la population traitable de groupes is not typically collected during initial medication trials. particuliers tels que les femmes enceintes, les enfants We present here a study done to compare the usage and et les personnes âgées a poussé les médecins à faire global effectiveness of two medications, Pregabalin and des choix entre les médicaments disponibles sur la base Lacosamide. 158 patients were administered Pregabalin de perception de la sécurité. Quelques informationst and 137 patients were administered Lacosamide. The clés qui pourraient guider le choix d’un médecin ne average initial frequency of complex partial seizures (CPS) sont généralement pas collectées lors des essais de for patients starting Pregabalin was 6 per month and 5.5 médicaments initiaux. -
Impact of Carbamazepine and Lacosamide on Serum Lipid Levels
Received: 19 November 2020 | Accepted: 12 January 2021 DOI: 10.1111/epi.16859 LETTER Impact of carbamazepine and lacosamide on serum lipid levels To the Editors: if the authors would have explored some subgroups in this We read with interest the recent article titled “Effects of post hoc analysis, such as whether those with elevated liver lacosamide and carbamazepine on lipids in a randomized transaminases, those receiving higher doses, and those hav- trial” by Mintzer et al.1 The authors have shown that carba- ing higher serum CBZ levels, as mentioned in the original mazepine (CBZ) elevates serum lipids, whereas lacosamide study results, had more significant dyslipidemia. Patients re- (LCM) does not affect lipids levels. We wish to add certain ceiving enzyme- inducing ASMs with certain CYP450 poly- points. morphisms are more likely to have more hepatic dysfunction The authors have used analysis of covariance to determine and dyslipidemia.5 As the authors have not performed any whether the difference between the two groups in terms of el- analysis for cytochrome P polymorphism, CRP, lipopro- evation of serum lipids was significantly different. However, tein (a), and other markers of atherosclerosis in the original in the results, they have not mentioned the variance explained study protocol, they could have explored the subgroup with by the independent variable (i.e., between- group variance) drug- induced transaminitis as a potentially high- risk group and unexplained variance (ie, within-g roup variance).2 It for having more dyslipidemia.6 Similarly, the authors should could have revealed how much of the difference in change of also have screened for whether the cases with well-contr olled lipid profile parameters between the LCM and CBZ groups epilepsy and uncontrolled epilepsy had any significant differ- was truly due to the effect of antiseizure medications (ASMs) ence in change in serum lipid levels. -
Product Update Price List Winter 2014 / Spring 2015 (£)
Product update Price list winter 2014 / Spring 2015 (£) Say to affordable and trusted life science tools! • Agonists & antagonists • Fluorescent tools • Dyes & stains • Activators & inhibitors • Peptides & proteins • Antibodies hellobio•com Contents G protein coupled receptors 3 Glutamate 3 Group I (mGlu1, mGlu5) receptors 3 Group II (mGlu2, mGlu3) receptors 3 Group I & II receptors 3 Group III (mGlu4, mGlu6, mGlu7, mGlu8) receptors 4 mGlu – non-selective 4 GABAB 4 Adrenoceptors 4 Other receptors 5 Ligand Gated ion channels 5 Ionotropic glutamate receptors 5 NMDA 5 AMPA 6 Kainate 7 Glutamate – non-selective 7 GABAA 7 Voltage-gated ion channels 8 Calcium Channels 8 Potassium Channels 9 Sodium Channels 10 TRP 11 Other Ion channels 12 Transporters 12 GABA 12 Glutamate 12 Other 12 Enzymes 13 Kinase 13 Phosphatase 14 Hydrolase 14 Synthase 14 Other 14 Signaling pathways & processes 15 Proteins 15 Dyes & stains 15 G protein coupled receptors Cat no. Product name Overview Purity Pack sizes and prices Glutamate: Group I (mGlu1, mGlu5) receptors Agonists & activators HB0048 (S)-3-Hydroxyphenylglycine mGlu1 agonist >99% 10mg £112 50mg £447 HB0193 CHPG Sodium salt Water soluble, selective mGlu5 agonist >99% 10mg £59 50mg £237 HB0026 (R,S)-3,5-DHPG Selective mGlu1 / mGlu5 agonist >99% 10mg £70 50mg £282 HB0045 (S)-3,5-DHPG Selective group I mGlu receptor agonist >98% 1mg £42 5mg £83 10mg £124 HB0589 S-Sulfo-L-cysteine sodium salt mGlu1α / mGlu5a agonist 10mg £95 50mg £381 Antagonists HB0049 (S)-4-Carboxyphenylglycine Competitive, selective group 1 -
Neuroscience Products
Neuroscience Products CATALOG CATALOG NUMBER U.S. $ NUMBER U.S. $ -A- 3-(N-ACETYLAMINO)-5-(N-DECYL-N- 1 mg 27.50 159549 METHYLAMINO)BENZYL ALCOHOL 5 mg 89.40 o A23187 0-5 C [103955-90-4] (ADMB) See: Antibiotic A23187 A Protein Kinase C activator. Ref.: Proc. Nat. Acad. Sci. USA, 83, 4214 AA-861 20 mg 72.70 (1986). 159061 Purity: 95% 100 mg 326.40 C20H34N2O2 MW 334.5 0oC Orally active, specific and potent inhibitor of 5-lipoxygenase. N-ACETYL-ASP-GLU 25 mg 45.00 153036 [3106-85-2] 100 mg 156.00 Ref.: 1. Yoshimoto, T., et.al., Biochim. o Biophys. Acta, 713, 470 (1982). 2. Ashida, -20-0 C An endogenous neuropeptide with high 250 mg 303.65 Y., et.al., Prostaglandins, 26, 955 (1983). 3. affinity for a brain "Glutamate" receptor. Ancill, R.J., et.al., J. Int. Med. Res., 18, 75 Ref: Zaczek, R., et al., Proc. Natl. Acad. (1990). Sci. (USA), 80, 1116 (1983). C21H26O3 MW 326.4 C11H16N2O8 MW 304.3 ABL PROTEIN TYROSINE KINASE 250 U 47.25 N-ACETYL-2-BENZYLTRYPTAMINE 195876 (v-abl) 1 KU 162.75 See: Luzindole -70oC Recombinant Expressed in E. coli ACETYL-DL-CARNITINE 250 mg 60.00 A truncated form of the v-abl protein 154690 [2504-11-2] 1 g 214.00 tyrosine kinase which contains the 0oC Hydrochloride minimum region needed for kinase activity Crystalline and fibroblast transformation. Suppresses C9H17NO4 • HCl MW 239.7 apoptosis and induces resistance to anti-cancer compounds. O-ACETYL-L-CARNITINE CHLORIDE 500 mg 11.45 Activity: 100 KU/ml 159062 [5080-50-2] 1 g 20.65 Unit Definition: one unit is the amount of 0-5oC (R-(-)-2-Acetyloxy-3-carboxy-N,N,N-trimethyl 5 g 97.45 enzyme which catalyzes the transfer of 1 -1-propanaminium chloride) pmol of phosphate to EAIYAAPFAKKK per Purity: >88% minute at 30°C, pH 7.5. -
Identifying Nootropic Drug Targets Via Large-Scale Cognitive GWAS and Transcriptomics
bioRxiv preprint doi: https://doi.org/10.1101/2020.02.06.934752; this version posted February 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Title: Identifying Nootropic Drug Targets via Large-Scale Cognitive GWAS and Transcriptomics Max Lam1, 2, 3,4, Chia-Yen, Chen3,5,6, Xia Yan7,8, W. David Hill9, 10, Joey W. Trampush11, Jin Yu1, Emma Knowles12,13,14, Gail Davies9, 10, Eli Stahl15, 16, Laura Huckins15, 16, David C. Liewald10, Srdjan Djurovic17, 18, Ingrid Melle18, 19, Andrea Christoforou20, Ivar Reinvang21, Pamela DeRosse1, 22, 23, Astri J. Lundervold24, Vidar M. Steen18, 20, Thomas Espeseth19, 21, Katri Räikkönen25, Elisabeth Widen26, Aarno Palotie26, 27, 28, Johan G. Eriksson29, 30, 31, Ina Giegling32, Bettina Konte32, Annette M. Hartmann32, Panos Roussos15, 16, 33, Stella Giakoumaki34, Katherine E. Burdick15, 33, 35, Antony Payton36, William Ollier37, 38, Ornit Chiba- Falek39, Deborah K. Koltai39, 40 , Anna C. Need41, Elizabeth T. Cirulli42, Aristotle N. Voineskos43, Nikos C. Stefanis44, 45, 46, Dimitrios Avramopoulos47, 48, Alex Hatzimanolis44, 45, 46, Nikolaos Smyrnis44, 45, Robert M. Bilder49, Nelson A. Freimer49, Tyrone D. Cannon50, 51, Edythe London49, Russell A. Poldrack52, Fred W. Sabb53, Eliza Congdon49, Emily Drabant Conley54, Matthew A. Scult55, Dwight Dickinson56, Richard E. Straub57, Gary Donohoe58, Derek Morris58, Aiden Corvin59, Michael Gill59, Ahmad R. Hariri55, Daniel R. Weinberger57, Neil Pendleton60, Panos Bitsios61, Dan Rujescu32, Jari Lahti25, 62, Stephanie Le Hellard18, 20, Matthew C. -
Chembridge Focused Ion Channel Core Plate 3408
Smal Molecule Library: ChemBridge Focused Ion Channel Core Plate 3408 Vendor Reagent Plate Well Targets Active Compound Scheme# ID 3408 A03 26558344 Potassium Channel Opener COC(=O)c1ccc(=O)n(CCNC(=O)c2ccccn2)c1 2225 3408 A04 74210071 Potassium Channel Opener Clc1ncc(cn1)NC(=O)c1ccc(Cl)c(F)c1 2218 3408 A05 38190270 Potassium Channel Modulator CC(=O)Nc1ccc2nc([nH]c2c1)c1ccccc1c1nc2ccccc2[nH]1 3512 3408 A06 41995970 Potassium Channel Opener Clc1ncc(cn1)NC(=O)c1ccc(Cl)c(F)c1 2218 3408 A07 54490250 Calcium Channel Blocker P-Type and L-Type COc1nsnc1c1cccc(c1)n1c(N)nc2ccccc12 2213 3408 A08 18950151 Potassium Channel Inhibitor CN(C)c1nc(NCc2ccccn2)c2c(occ2c2ccccc2)n1 3504 3408 A09 96447557 Calcium Channel Blocker COc1ccc2c(ncn2c2cccc(c2)c2ccccc2)c1 3507 3408 A10 62301407 Potassium Channel Opener Clc1ncc(cn1)NC(=O)c1ccc(Cl)c(F)c1 2225 3408 A11 27997194 Calcium Channel Blocker N-type O=C(NC1CCN(CC1)Cc1ccccc1)[C@H](CSCC1CCCCC1)NC(=O)[C@@H]1CSCN1C(=O)CC(C)(C)C 2225 3408 A12 21908544 Potassium Channel Activator O=c1ccccn1C1=CC(C)(C)Oc2cc3nonc3cc12 3232 3408 A13 44857539 Potassium Channel Activator CC(=O)Nc1ccc(cn1)NC(=S)NC(C)C(C)(C)C 2225 3408 A14 72294470 Potassium Channel Inhibitor COCCOc1nc(NCc2ccccn2)c2c(occ2c2ccccc2)n1 3504 3408 A15 61280668 Calcium and Sodium Channel Blocker 2202 3408 A16 62460131 Potassium Channel Activator COc1ccc[n+]([O-])c1C1=NC(C)(C)Oc2ccc(cc12)C(F)(F)F 3512 3408 A17 67807991 Potassium Channel Modulator Clc1ccc(cn1)NC(=O)c1ccc(Cl)c(c1)C(F)(F)F 3505 3408 A18 35932100 Potassium Channel Blocker CCCN1C(=O)C(NC(=O)Cc2cccc3ccccc23)N=C(N2CCCCC2)c2ccccc12 -
Lacosamide Action on Sodium Channels
astrocytes [Ding et aI., J Neurosci, 2007]. Astrocytic cytes are not able anymore to dock the dendrites prop dysfunction in epilepsy is associated with profound erly. Taken together, the state of the art points to astro structural changes: in rat, epileptic discharges follow cytes as a potential target of therapy in epilepsy. ing mechanical brain damage or in the kainate model are correlated with the loss of micro domain organiza Supported by the Ministry of Science and Education of Poland. tion [Oberheim et aI., J Neurosci, 2008]. Hence, astro- grant no S 005/P-N/2007/01. Lacosamide action on sodium channels Marcin Balcerzak UCB Pharma/VEDIM Sp. z 0.0., Medical Affairs Department, Warszawa, Poland Lacosamide ((R)-2-acetamido-N-benzyl-3-methoxy which inhibited firing within about 100 ms after burst propionamide) is a D-serine derivative approved as an initiation [Errington et aI., Mol Pharmacol, 2008]. antiepileptic drug (AED) in adjunctive therapy of These results suggest that the mechanism of action of partial-onset seizures. Lacosamide acts on voltage lacosamide is different from other anticonvulsive so dependent sodium channels responsible for action po dium channel blockers. tential initiation and propagation. Sodium channels In addition to fast inactivation, another mechanism can exist in different conformations depending on cell of sodium channel modulation discovered in 1978 membrane potential and accounting for specific func [Rudy et aI., J Physiol, 1978] likely involves channel tional states. Membrane depolarization causes sodium structural rearrangement that occurs under conditions channels to transition from a resting to an open state, of slight depolarization and prolonged repetitive fir allowing sodium ion influx according to the electro ing. -
Effect of Pentobarbital on Ph and Electrolyte Levels After Induced Seizure in Rats
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Seizure (2007) 16, 397—401 www.elsevier.com/locate/yseiz Effect of pentobarbital on pH and electrolyte levels after induced seizure in rats R. Uribe-Escamilla a, D. Mota-Rojas b,P.Sa´nchez-Aparicio b, M. Alonso-Spilsbury b, R. Gonza´lez-Pin˜a c, A. Alfaro-Rodrı´guez a,* a Laboratory of Neurochemistry, National Institute of Rehabilitation, SSA, Me´xico City, Mexico b Department of Animal Production and Agriculture, Universidad Auto´noma Metropolitana-Xochimilco, Me´xico City, Mexico c Laboratory of Neuroplasticity of National Institute of Rehabilitation, SSA, Me´xico City, Mexico Received 29 November 2006; received in revised form 25 January 2007; accepted 20 February 2007 KEYWORDS Summary We studied the effects of high doses of pentobarbital (PB) and carba- Pentobarbital; mazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pento- Pentylenetetrazole; barbital decreased Ca2+ and Na+ levels without pentylenetetrazole (PTZ). After this, Carbamazepine; Ca2+ and Na+ levels continued to decrease except when CBZ was used, which Electrolytes preserved the Ca2+ levels PTZ may have opposed effects on PB. Our results suggest that PB causes changes in electrolyte levels and pH, but these changes are diminished by CBZ. # 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. Introduction The conditions grouped under the term epilepsy constitute an area of continuing medical need. It has One of 11 people has epilepsy problems, experiencing been estimated that about 20% of the patients with at least one seizure at some points. -
(12) United States Patent (10) Patent No.: US 9.482,672 B2 Gong Et Al
USOO9482672B2 (12) United States Patent (10) Patent No.: US 9.482,672 B2 Gong et al. (45) Date of Patent: Nov. 1, 2016 (54) METHODS FOR DIAGNOSING IRRITABLE 2002fO197661 A1 12/2002 Niles et al. BOWEL, SYNDROME 2003,022903.0 A1 12/2003 Theoharides 2008.OO57590 A1 3/2008 Urdea et al. (71) Applicant: NESTEC S.A., Vevey (CH) 2008/0085524 A1 4/2008 Lois (72) Inventors: Hua Gong, San Diego, CA (US); Shui FOREIGN PATENT DOCUMENTS Long Wang, San Diego, CA (US); JP 2000-065820 A 3, 2000 Sharat Singh, Rancho Santa Fe, CA JP 2003-277378. A 10, 2003 (US) JP 2007-506100 A 3, 2007 JP 2007-1864.57 A 7/2007 JP 2008-521817. A 6, 2008 (73) Assignee: Nestec S.A., Vevey (CH) JP 2008-530537 A 8, 2008 JP 2009-52.1690 A 6, 2009 (*) Notice: Subject to any disclaimer, the term of this WO O3.011812 A1 2, 2003 patent is extended or adjusted under 35 WO 2005/O29091 A2 3, 2005 U.S.C. 154(b) by 0 days. WO 2007/076411 A1 7/2005 WO 2006/06877O A1 6, 2006 WO 2006/084.299 A2 8, 2006 (21) Appl. No.: 14/222,531 WO 2008/O14414 A2 1, 2008 WO 2008/022177 A2 2, 2008 (22) Filed: Mar. 21, 2014 WO 2009,045291 A2 4/2009 (65) Prior Publication Data OTHER PUBLICATIONS US 2014/O1997.09 A1 Jul. 17, 2014 Jones et al. The Lancet, vol. 320, Issue 8308, pp. 1115-1172, Nov. 20, 1982, Abstract Only.* Related U.S. Application Data Thevarajah et al.