3,3-Bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (BHMI), the active metabolite of the laxative sulisatin.
The disodium salt of the sulphuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (sodium sulisatin, Laxitex), a synthetic laxative with two phenolic groups esterified with sulfate, has been studied in order to find out if its laxative properties may be attributed to the unaltered compound or to its diphenolic derivative BHMI. We first studied the effect of homogenates of the gastrointestinal tract of rats and of rat cecal content of the hydrolysis of sulfate ester bonds of sulisatin. Results show that sulisatin can be hydrolyzed by cecal content while homogenates of stomach, small intestine and large intestine have no hydrolytic effect. Sulisatin is also a substrate of arylsulfate sulphohydrolase obtained from the snail Helix pomatia. The unaltered drug has no effect on the intestinal motility since it does not change the intestinal transit speed in rats pretreated with neomycin sulfate. Sulisatin (1.5, 3 and 6 mg) is unable to inhibit water absorption in rat colon while small amounts of BHMI (15 and 30 micrograms) may inhibit it significantly. It is concluded that sulisatin passes unaltered through the small intestine and is hydrolyzed in the large intestine by the intestinal microflora to its diphenolic derivative BHMI, which is responsible for the laxative activity of the drug.
D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D001711:Biotransformation; D002400:Cathartics / Q000378:metabolism* / Q000494:pharmacology; D005243:Feces / Q000032:analysis; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D010636:Phenols / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D002400:Cathartics; D007211:Indoles; D010636:Phenols; D001192:Arylsulfatases; D009355:Neomycin