Brivaracetam and seletracetam, two new SV2A ligands, improve paroxysmal dystonia in the dt sz mutant hamster.
Previous examinations demonstrated antidystonic effects of the synaptic vesicle protein 2A (SV2A) ligand levetiracetam in the dt(sz) mutant hamster, an animal model of paroxysmal non-kinesiogenic dyskinesia in which dystonic episodes can be induced by stress. In the present study, we examined the effects of the two new, high affinity SV2A ligands, brivaracetam and seletracetam, in comparison to levetiracetam on the severity of dystonia in mutant hamsters. Seletracetam (50 and 75 mg/kg i.p.) and brivaracetam (75 mg/kg i.p.) reduced the severity of dystonia to a comparable extent as levetiracetam (50 and 75 mg/kg i.p.). These data confirm the therapeutic potential of these pyrrolidone derivatives for the treatment of paroxysmal dystonia.
Hamann
Melanie
M
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14195 Berlin, Germany.
Sander
Svenja E
SE
Richter
Angelika
A
D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000188:drug therapy*; D006801:Humans; D000077287:Levetiracetam; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index
D008024:Ligands; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011760:Pyrrolidinones; C518915:Seletracetam; C076414:SV2A protein, human; D000077287:Levetiracetam; C482793:brivaracetam; D010889:Piracetam