Comparison of the Anticonvulsant Activities of Ethosuximide, Valproate, and a New Anticonvulsant, Thiobutyrolactone

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Abstract
Anticonvulsant properties of .alpha.-ethyl-.alpha.-methyl-.gamma.-thiobutyrolactone (.alpha.-EMTBL) were compared with those of the antiepileptic drugs ethosuximide (ESM) and valproate (VPA) by testing their ability to block seizures in mice caused by maximal electroshock (MES), pentylenetetrazol (PTZ), picrotoxin (PICRO), bicuculline (BIC), methyl-6,7-dimethoxy-4-ethyl-.beta.-carboline-3-carboxylate (DMCM), N-methyl-D,L-aspartate (NMDA), aminophylline (AMPH), strychnine (STR). .beta.-ethyl-.beta.-methyl-.gamma.-thiobutyrolactone (.beta.-EMTBL), and t-butylbicyclophosphorothnionate (TBPS). ESM was able to prevent PTZ-, PICRO-, DMCM-, and .beta.-EMTBL-induced seizures. In contrast, VPA and .alpha.-EMTBL blocked all of these plus MES-, TBPS-, and BIC-induced convulsions. Only VPA prevented AMPH-induced seizures. None of the anticonvulsants blocked STR or NMDA seizures. Rotorod testing for acute neurotoxicity demonstrated that ESM was the least toxic and .alpha.-EMTBL and VPA were equivalent. Animals treated daily with high doses of .alpha.-EMTBL for a 2-week period appeared healthier and had a higher survival rate than animals treated with VPA in the same manner. After a single intraperitoneal (i.p.) injection, the duration of anticonvulsant action of .alpha.-EMTBL was 1.3 and 4 times longer than that of ESM and VPA, respectively. These results indicate that .alpha.-EMTBL has a wide spectrum of anticonvulsant action like VPA but may be less toxic and longer acting. We suggest that .alpha.-EMTBL is a compound worthy of further testing and development as an antiepileptic drug (AED).