The anticonvulsive actions of two lipophilic taurine derivatives

The taurine derivatives, 2-phthalimidoethanesulfon-N-isopropylamide (taltrimide) and 2-phthalimidoethanesulfonamide (MY-103), were tested intraperitoneally against genetic and experimentally produced seizures. In the genetically seizure-susceptible rat, taltrimide raised the threshold for audiogenic seizures and decreased seizure severity. MY-103 decreased seizure intensity in maximally-responding animals, but was otherwise without effect on sound-induced seizures. Taltrimide had a greater potency against maximal as compared to minimal seizures, and, at 150 mg/kg, it completely suppressed clonic and myoclonic seizures induced by intracerebroventricular injections of guanidinoethane sulfonate (9.2 ?mol) in rats. MY-103, at doses up to 300 mg/kg, was ineffective against guanidinoethane sulfonate-induced seizures. In pentylene tetrazole-induced seizures in the rat, taltrimide (300 mg/kg) raised the threshold for seizures from 80 mg/kg pentylene tetrazole to 115 mg/kg. Taltrimide also raised the threshold for lead-exacerbated pentylene tetrazole-induced seizures. Taurine, being more lipophobic than taltrimide, was ineffective on intraperitoneal administration against pentylene tetrazole-induced seizures. The more lipophilic beta-alanine (8 mmol/kg) raised pentylene tetrazole-seizure threshold on intraperitoneal administration. Thus, lipophilic phthalimido analogs of taurine are effective on peripheral administration against both genetic and experimentally-induced seizures.