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  • Title: Comparison of the anticonvulsant activities of ethosuximide, valproate, and a new anticonvulsant, thiobutyrolactone.
    Author: Ferrendelli JA, Holland KD, McKeon AC, Covey DF.
    Journal: Epilepsia; 1989; 30(5):617-22. PubMed ID: 2507307.
    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-butylbicyclophosphorothionate (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 MESTBPS-, 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).
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