Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats.
The novel anticonvulsant drug ucb L059 ((S)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide) was evaluated in several rodent models of partial and generalized seizures. Ucb L059 (27-108 mg/kg i.p.) increased the thresholds for tonic electroconvulsions and myoclonic and clonic seizures induced by timed i.v. infusion of pentylenetetrazol (PTZ), but was ineffective in the traditional maximal electroshock seizure and s.c. PTZ seizure tests in mice and rats in doses up to 500 mg/kg. The anticonvulsant potency of ucb L059 in seizure threshold tests was similar to that of standard drugs, such as valproate. In amygdala-kindled rats, ucb L059 exerted potent anticonvulsant activity against both focal and secondarily generalized seizures at doses of 13-108 mg/kg. The adverse effects of ucb L059 were quantitated in the open field and in standard tests for motor impairment, such as the rotarod and chimney tests. Ucb L059 exerted only minimal effects on behaviour, e.g. slight hyperactivity, and did not impair muscle activity in the rotarod test in doses up to 1700 mg/kg i.p. The data indicate that ucb L059 is an interesting new anticonvulsant agent with a broad spectrum of activity and high therapeutic index.
Löscher
W
W
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Hönack
D
D
D000679:Amygdala / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D004597:Electroshock; D004828:Epilepsies, Partial / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D007696:Kindling, Neurologic / Q000502:physiology; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D009207:Myoclonus / Q000139:chemically induced / Q000503:physiopathology; D010433:Pentylenetetrazole; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques
D000927:Anticonvulsants; D000077287:Levetiracetam; D010433:Pentylenetetrazole; D010889:Piracetam