Anticonvulsant profile of valrocemide (TV1901): a new antiepileptic drug.
OBJECTIVE
We sought to investigate the anticonvulsant activity of the new antiepileptic drug (AED), valrocemide or TV1901 (VGD) in various animal (rodent) models of human epilepsy to determine its anticonvulsant profile and safety margin.


METHODS
VGD was administered intraperitoneally to CF no. 1 mice and orally or intraperitoneally to Sprague-Dawley rats. The anticonvulsant activity of VGD was examined in nine different animal models of epilepsy for its ability to block electrically, chemically, or sensorily induced seizures.


RESULTS
In mice VGD afforded complete protection against maximal electroshock (MES)-, pentylenetetrazole-, picrotoxin-, and bicuculline-induced seizures and 6-Hz "psychomotor" seizures with median effective dose (ED50) values of 151, 132, 275, 248, and 237 mg/kg, respectively. VGD was also effective in preventing sound-induced seizures in Frings audiogenic-seizure susceptible mice (ED50, 52 mg/kg). The median neurotoxic dose in mice was 332 mg/kg. After oral administration to rats, VGD was active in the MES test, with an ED50 of 73 mg/kg, and the median neurotoxic dose was 1,000 mg/kg. Intraperitoneal administration of 300 mg/kg of VGD to hippocampal kindled Sprague-Dawley rats blocked generalized seizures and shortened the afterdischarge duration significantly. VGD also provided complete protection from focal seizures in the corneally kindled rats (ED50,161 mg/kg).


CONCLUSIONS
The results obtained in this study suggest that VGD has a broad spectrum of anticonvulsant activity and promising potential as a new AED.
Isoherranen
N
N
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Woodhead
J H
JH
White
H S
HS
Bialer
M
M
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D004827:Epilepsy / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D020195:Epilepsy, Reflex / Q000517:prevention & control; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*
D000927:Anticonvulsants; C108894:TV 1901; D005998:Glycine; D010433:Pentylenetetrazole