Anticonvulsant activity of paeonimetabolin-I adducts obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis

Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of diaste reoisomers after incubation of paeoniflorin with Lactobacillus brevis in th e presence of various thiols. The anticonvulsant activity of the adducts wa s investigated in mice using the maximal subcutaneous pentylenetetrazol sei zure test and sodium valproate (1.5 mmol/kg) as a positive control. Thirtee n adducts showed dose-dependent prolongation of latencies of clonic and ton ic convulsions. Maximal protection against convulsions was effectively demo nstrated by 8-(n-hexylthio)paeonimetabolin I (8) and 8-benzoylthiopaeonimet abolin I (18) at doses of 0.125 and 0.25 mmol/kg, respectively, while 100% protection was only achieved at 0.5 mmol/kg of 8-cyclopentylthiopaeonimetab olin I and 8-(p-tolylthio)paeonimetabolin I. The principal anticonvulsant a ctivity of the diastereoisomers of 8 and 18 was attributed to their 7S-isom ers [ED50 values of 0.09 and 0.12 mmol/kg, and protective indices of 5.0 an d 4.0 for 8 (7S) and 18 (7S), respectively], while the 7R counterparts [8 ( 7R) and 18 (7R)] showed a muscle relaxation effect.