Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 4 of 4
Full-Text Articles in Life Sciences
Adjunctive Perampanel For Refractory Partial-Onset Seizures. Randomized Phase Iii Study 304, Jacqueline A. French, Gregory L. Krauss, Victor Biton, David Squillacote, Haichen Yang, Antonio Laurenza, Dinesh Kumar, Michael A. Rogawski
Adjunctive Perampanel For Refractory Partial-Onset Seizures. Randomized Phase Iii Study 304, Jacqueline A. French, Gregory L. Krauss, Victor Biton, David Squillacote, Haichen Yang, Antonio Laurenza, Dinesh Kumar, Michael A. Rogawski
Michael A. Rogawski
Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. Methods:This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1–3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder …
Characterization Of Seizures Induced By Acute And Repeated Exposure To Tetramethylenedisulfotetramine, Dorota Zolkowska, Christopher N. Banks, Ashish Dhir, Bora Inceoglu, James R. Sanborn, Mark R. Mccoy, Donald A. Bruun, Bruce D. Hammock, Pamela J. Lein, Michael A. Rogawski
Characterization Of Seizures Induced By Acute And Repeated Exposure To Tetramethylenedisulfotetramine, Dorota Zolkowska, Christopher N. Banks, Ashish Dhir, Bora Inceoglu, James R. Sanborn, Mark R. Mccoy, Donald A. Bruun, Bruce D. Hammock, Pamela J. Lein, Michael A. Rogawski
Michael A. Rogawski
Tetramethylenedisulfotetramine (tetramine; TETS) is a potent convulsant poison that is considered to be a chemical threat agent. To provide a basis for the investigation of antidotes for TETS-induced seizures, we characterized the convulsant activity of TETS in mice and rats when administered by the intraperitoneal, intravenous, oral and intraventricular routes as a single acute dose and with repeated sublethal doses. In mice, parenteral and oral TETS caused immobility, myoclonic body jerks, clonic seizures of the forelimbs and/or hindlimbs, tonic seizures and death. The CD50 values for clonic and tonic seizures following oral administration were 0.11 and 0.22 mg/kg, respectively. Intraventricular …
Role Of Neurosteroids In The Anticonvulsant Activity Of Midazolam, Ashish Dhir, Michael A. Rogawski
Role Of Neurosteroids In The Anticonvulsant Activity Of Midazolam, Ashish Dhir, Michael A. Rogawski
Michael A. Rogawski
BACKGROUND AND PURPOSE Midazolam is a short-acting benzodiazepine that is widely used as an intravenous sedative and anticonvulsant. Besides interacting with the benzodiazepine site associated with GABA-A receptors, some benzodiazepines act as agonists of translocator protein (18 kDa) (TSPO) to enhance the synthesis of steroids, including neurosteroids with positive modulatory actions on GABA-A receptors. We sought to determine if neurosteroidogenesis induced by midazolam contributes to its anticonvulsant action. EXPERIMENTAL APPROACH Mice were pretreated with neurosteroid synthesis inhibitors and potentiators followed by midazolam or clonazepam, a weak TSPO ligand. Anticonvulsant activity was assessed with the intravenous pentylenetetrazol (PTZ) threshold test. KEY …
Propofol Hemisuccinate Suppresses Cortical Spreading Depression, Ashish Dhir, Christoph Lossin, Michael A. Rogawski
Propofol Hemisuccinate Suppresses Cortical Spreading Depression, Ashish Dhir, Christoph Lossin, Michael A. Rogawski
Michael A. Rogawski
Propofol is a rapidly acting water-insoluble non-barbiturate anesthetic agent that is widely used as an intravenous sedative-hypnotic agent. Anecdotal evidence indicates that propofol may be effective at terminating intractable migraine headache. Cortical spreading depression (CSD) is believed to be the neural correlate of migraine aura and may be a trigger for migraine pain. Agents that block the induction or slow the spread of CSD may be of utility in treating migraine. Here we examined the ability of propofol hemisuccinate (PHS), a water-soluble prodrug of propofol, to affect CSD in mice. For comparison, we examinined dizocilpine, an NMDA receptor antagonist, that …