7α-Thiomethylspironolactone
7α-Thiomethylspironolactone is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and the major active metabolite of spironolactone. Other important metabolites of spironolactone include 7α-thiospironolactone, 6β-hydroxy-7α-thiomethylspironolactone, and canrenone.
Spironolactone is a prodrug with a short terminal half-life of 1.4 hours. The active metabolites of spironolactone have extended terminal half-lives of 13.8 hours for 7α-TMS, 15.0 hours for 6β-OH-7α-TMS, and 16.5 hours for canrenone, and accordingly, these metabolites are responsible for the therapeutic effects of the drug.
7α-TS and 7α-TMS have been found to possess approximately equivalent affinity for the rat ventral prostate androgen receptor relative to that of spironolactone. The affinity of 7α-TS, 7α-TMS, and spironolactone for the rat prostate AR is about 3.0 to 8.5% of that of dihydrotestosterone.
7α-TMS has been found to account for around 80% of the potassium-sparing effect of spironolactone, whereas canrenone accounts for the remaining approximate 10 to 25% of the potassium-sparing effect of the drug.
