Ralitoline (CI-946) and CI-953 block sustained repetitive
sodium action potentials in cultured mouse spinal cord neurons and
displace batrachotoxinin A 20-[alpha]-benzoate binding in
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- Macdonald, Robert L. McLean, Michael J. Rock, David M. Taylor, Charles P. Catterall, William A.
- Department of Neurology, University of Michigan,
Neuroscience Laboratory, Ann Arbor, MI, U.S.A. Department of Pharmacology, Parke-Davis
Pharmaceutical Research Division, Warner Lambert Company, Ann
Arbor, MI, U.S.A. Department of Pharmacology, University of
Washington School of Medicine, Seattle, WA, U.S.A.
- Ralitoline and CI-953 are anticonvulsant compounds
active in both maximal electroshock and kindling models of seizures
with rodents. CI-953 (IC50 = 5 [mu]M) and ralitoline (IC50 = 2
[mu]M) both blocked sustained repetitive firing of sodium action
potentials with effects on firing activity triggered by spontaneous
excitatory postsynaptic potentials at higher concentrations. No
effects on iontophoretic GABA and glutamate responses were noted.
Both compounds inhibited the binding of tritiated batrachotoxinin A
20-[alpha]-benzoate ([3H]BTX-b) to rat brain synaptosomes with
apparent Kd values of 29 [mu]M (CI-953) and 25 [mu]M (ralitoline).
Our results suggest that effects on voltage-dependent sodium
channels may underlie the anticonvulsant action of these
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