7α-Thiospironolactone
7α-Thiospironolactone is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and a minor active metabolite of spironolactone. Other important metabolites of spironolactone include 7α-thiomethylspironolactone, 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-TS, via a reactive metabolite formed by 17α-hydroxylase, is a suicide inhibitor of 17α-hydroxylase, and is thought to be involved in the inhibition of 17α-hydroxylase by spironolactone.
| Compound | Cmax | Cmax | AUC | t1/2 |
| Spironolactone | 72 | 80 | 231 | 1.4 |
| Canrenone | 155 | 181 | 2173 | 16.5 |
| 359 | 391 | 2804 | 13.8 | |
| 101 | 125 | 1727 | 15.0 |
A study assessed the interaction of spironolactone and 7α-TS with sex hormone-binding globulin and found that they had very low affinity for this carrier protein.