Anticonvulsant profile of the neuroactive steroid, SGE-516, in animal models

التفاصيل البيبلوغرافية
العنوان: Anticonvulsant profile of the neuroactive steroid, SGE-516, in animal models
المؤلفون: Francesco G. Salituro, Gabriel Martinez Botella, James J. Doherty, Rebecca S. Hammond, Alison L. Althaus, Carla Maciag, Albert J. Robichaud, Michael A. Ackley
المصدر: Epilepsy Research. 134:16-25
بيانات النشر: Elsevier BV, 2017.
سنة النشر: 2017
مصطلحات موضوعية: Male, 0301 basic medicine, Allosteric modulator, Neuroactive steroid, medicine.medical_treatment, Action Potentials, Convulsants, Pregnanolone, Pharmacology, Hippocampus, Rats, Sprague-Dawley, Fragile X Mental Retardation Protein, Mice, 03 medical and health sciences, Epilepsy, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Seizures, Convulsion, Kindling, Neurologic, Potassium Channel Blockers, medicine, Animals, gamma-Aminobutyric Acid, Mice, Knockout, Electroshock, GABAA receptor, Allopregnanolone, medicine.disease, Rats, Disease Models, Animal, 030104 developmental biology, Anticonvulsant, Neurology, Mechanism of action, chemistry, Pentylenetetrazole, Anticonvulsants, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery
الوصف: Despite the availability of multiple antiepileptic drugs (AED), failure to adequately control seizures is a challenge for approximately one third of epilepsy patients, and new therapies with a differentiated mechanism of action are needed. The neuroactive steroid, SGE-516, is a positive allosteric modulator of both gamma- and delta-containing GABAA receptors. This broad GABAA receptor activity differentiates neuroactive steroids like SGE-516 from benzodiazepines, a class of anticonvulsants which have been shown in vitro to selectively target gamma-subunit containing GABAA receptors. As a neuroactive steroid, SGE-516 has pharmacokinetic properties that are intended to allow for chronic oral dosing. We investigated the anticonvulsant activity of SGE-516 across numerous in vitro and in vivo models of seizure activity. SGE-516 dose-dependently reduced neuronal firing rates and epileptiform activity in vitro. In mice, SGE-516 protected against acute seizures in the PTZ-induced chemo-convulsant seizure model and the 6Hz psychomotor seizure model. In addition, SGE-516 demonstrated anticonvulsant activity in the mouse corneal kindling model. These data suggest that SGE-516 may have potential for development as a novel oral AED for the treatment of refractory seizures.
تدمد: 0920-1211
DOI: 10.1016/j.eplepsyres.2017.05.001
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2ebdf33e1a2544115114f31f08ce039
https://doi.org/10.1016/j.eplepsyres.2017.05.001
Rights: CLOSED
رقم الانضمام: edsair.doi.dedup.....e2ebdf33e1a2544115114f31f08ce039
قاعدة البيانات: OpenAIRE
الوصف
تدمد:09201211
DOI:10.1016/j.eplepsyres.2017.05.001