Similar effects of ralitoline and phenytoin on papillary muscle action potentials: evidence for sodium antagonistic activity.
Ralitoline is a new anticonvulsant, the profile of which most closely resembles that of phenytoin. Using papillary muscles isolated from guinea pig hearts, action potentials (APs) were elicited (0.5 Hz) and measured intracellularly. No significant effects on resting membrane potential, AP duration, and AP amplitude were observed up to 100 microM with both drugs. Ralitoline reduced dV/dtmax at 10 microM by 13% and at 100 microM by 45%; the effects of phenytoin were 5% and 15%, respectively. Thus, ralitoline and phenytoin exert sodium antagonistic effects. Related to the anticonvulsive concentrations seem in rodent brain, the inhibition of voltage-dependent sodium channels, which is primarily the suggested mechanism of action of phenytoin, may contribute to the anticonvulsive activity of ralitoline.
Wagner
B
B
Gödecke Research Institute, Freiburg, FRG.
Strumpf
G
G
Bartoszyk
G D
GD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009132:Muscles / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology*; D012964:Sodium / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology*
D000927:Anticonvulsants; D013844:Thiazoles; D010672:Phenytoin; D012964:Sodium; C054894:Ralitoline