U-54494A reduces 4-AP-induced afterdischarges of CA1 pyramidal cells in the hippocampal slice of the rat.
The anticonvulsant activity of U-54494A was studied in a 4-aminopyridine (4-AP) epilepsy model using extracellular recordings in in vitro hippocampal slices. Field potentials were evoked by stimulation of Schaffer collaterals, and recorded from the CA1 region of the hippocampus after infusion of 4-AP in the absence and presence of U-54494A. The number and the total area of after discharges (AD) in the presence of 4-AP were significantly decreased by increasing concentrations of U-54494A. In contrast, U-54494A did not significantly change the latency, duration, or area of the evoked PS in this paradigm. Phenytoin, a standard anticonvulsant, decreased the PS area without affecting either the PS latency or duration, or the AD number or area in the same paradigm. These present results provide more evidence that U-54494A is a novel and effective anticonvulsant that may be useful in the treatment of paroxysmal activity, without having generalized depressive effects.
Camacho-Ochoa
M
M
CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
VonVoigtlander
P F
PF
Hoffmann
W E
WE
Piercey
M P
MP
D015761:4-Aminopyridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D010672:Phenytoin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*
D000927:Anticonvulsants; D011759:Pyrrolidines; D010672:Phenytoin; D015761:4-Aminopyridine; C054216:U 54494A; D011188:Potassium; D002118:Calcium