title: Brivaracetam is superior to levetiracetam in a rat model of post-hypoxic myoclonus.
abstract: In the present study, we evaluated the anti-seizure and anti-myoclonic activity of levetiracetam and brivaracetam in an established rat model of cardiac arrest-induced post-hypoxic myoclonus. We found that brivaracetam (0.3 mg/kg, the minimal effective dose) was more potent than levetiracetam (3 mg/kg, the minimal effective dose) against post-hypoxic seizures. The anti-seizure activity of both compounds occurred 30 min following intraperitoneal (i.p.) administration and was maintained over the entire 150 min post-dose observation period. Both brivaracetam and levetiracetam significantly reduced auditory stimulated post-hypoxic myoclonus from a dose 0.3 mg/kg. At that dose, the anti-myoclonic activity of brivaracetam was already maximal whereas it continued to increase in a dose-relation manner with levetiracetam, suggesting that brivaracetam is a more potent agent. The onset and the duration of anti-myoclonic activity of both compounds were similar. These findings demonstrate that brivaracetam possesses more potent anti-seizure and anti-myoclonic activity than levetiracetam in an established rat model of cardiac arrest-induced post-hypoxic myoclonus.
authors: Long Beach Memorial Medical Center, The Parkinson's and Movement Disorder Research Laboratory, Long Beach, California 90806, USA. kktai@yahoo.com
authors: K-K
authors: KK
authors: Tai
authors: D D
authors: DD
authors: Truong
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004831:Epilepsies, Myoclonic / Q000188:drug therapy* / Q000209:etiology; D006323:Heart Arrest / Q000150:complications; D000860:Hypoxia / Q000209:etiology; D000077287:Levetiracetam; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011760:Pyrrolidinones / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
chemical_list: D000927:Anticonvulsants; D011760:Pyrrolidinones; D000077287:Levetiracetam; C482793:brivaracetam; D010889:Piracetam
references: J Cereb Blood Flow Metab. 1995 Mar;15(2):248-58
references: 7860659
references: Seizure. 2006 Apr;15(3):214-8
references: 16420982
references: Arch Neurol. 1975 May;32(5):304-7
references: 806277
references: Neurology. 2001 Feb 13;56(3):411-2
references: 11171914
references: N Engl J Med. 1978 Aug 10;299(6):313-4
references: 351404
references: Eur J Pharmacol. 2006 Apr 24;536(1-2):102-8
references: 16556440
references: Adv Neurol. 1986;43:157-69
references: 3080849
references: Brain Res. 2005 Oct 19;1059(2):122-8
references: 16197930
references: J Med Chem. 2004 Jan 29;47(3):530-49
references: 14736235
references: Mov Disord. 2000;15 Suppl 1:26-30
references: 10755269
references: Neurology. 2004 May 25;62(10 ):1879-81
references: 15159501
references: Epileptic Disord. 2000 Dec;2(4):209-12
references: 11174151
references: Epilepsia. 2001;42 Suppl 4:13-8
references: 11564119
references: Epilepsy Res. 1998 Jan;29(2):147-54
references: 9477147
references: Seizure. 2003 Dec;12(8):617-20
references: 14630506
references: Epilepsy Res. 2006 Sep;71(1):32-9
references: 16814521
references: Epilepsy Res. 2006 Jun;69(3):273-94
references: 16621450
references: Neurosci Lett. 2001 Jun 22;306(1-2):5-8
references: 11403944
references: Adv Neurol. 1979;26:49-84
references: 229719
references: Adv Neurol. 2002;89:295-306
references: 11968456
references: Curr Opin Investig Drugs. 2005 Jul;6(7):740-6
references: 16044671
references: Br J Pharmacol. 2002 Jul;136(5):659-72
references: 12086975
references: Epilepsia. 2002 Jan;43(1):9-18
references: 11879381
references: Mov Disord. 1994 Mar;9(2):201-6
references: 8196684
references: Mov Disord. 2000;15 Suppl 1:31-8
references: 10755270
references: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6
references: 15210974
references: Clin Neurosci. 1995-1996;3(4):236-45
references: 8891397