3-Hydroxymethylphenytoin valproic acid ester, a new prodrug combining two anticonvulsant drugs.
3-Hydroxymethylphenytoin valproic acid ester (VAL-PHT) was designed as a new prodrug combining valproic acid and phenytoin, two anticonvulsant drugs with different pharmacological profiles. The compound was hydrolyzed by rat plasma esterases in vitro but exhibited only activity in the maximal electroshock seizure test (MES test) after intraperitoneal administration to mice. The compound did not protect against pentylenetetrazole-induced seizures. It is concluded that VAL-PHT acts as a prodrug displaying the anticonvulsant profile of phenytoin.
Scriba
G K
GK
Department of Pharmaceutical Chemistry, University of Münster, Germany.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D003292:Convulsants; D004597:Electroshock; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D010672:Phenytoin / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
C104864:3-hydroxymethylphenytoin valproic acid ester; D000927:Anticonvulsants; D003292:Convulsants; D011355:Prodrugs; D014635:Valproic Acid; D010672:Phenytoin; D010433:Pentylenetetrazole