6β-Hydroxy-7α-thiomethylspironolactone explained

6β-Hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS) is a steroidal antimineralocorticoid of the spirolactone group and a major active metabolite of spironolactone.^{[1] [2] [3]} Other important metabolites of spironolactone include 7α-thiospironolactone (7α-TS; SC-24813), 7α-thiomethylspironolactone (7α-TMS; SC-26519), and canrenone (SC-9376).^{[4] [5] [6]}

Spironolactone is a prodrug with a short terminal half-life of 1.4 hours.^{[7] [8] [9]} 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.

6β-Hydroxytestosterone, which is analogous to 6β-OH-7α-TMS, has been found to possess virtually no androgenicity.^[10]

See also

• 7α-Thioprogesterone

Further reading

• Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, Stubbs K, Smith M, Karim A . Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites . J Clin Pharmacol . 29 . 4 . 342–7 . 1989 . 2723123 . 10.1002/j.1552-4604.1989.tb03339.x. 29457093 .

Notes and References

1. Yang J, Young MJ . Mineralocorticoid receptor antagonists-pharmacodynamics and pharmacokinetic differences . Curr Opin Pharmacol . 27 . 78–85 . 2016 . 26939027 . 10.1016/j.coph.2016.02.005 .
2. Kolkhof P, Bärfacker L . 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development . J. Endocrinol. . 234 . 1 . T125–T140 . 2017 . 28634268 . 5488394 . 10.1530/JOE-16-0600 .
3. Doggrell SA, Brown L . The spironolactone renaissance . Expert Opin Investig Drugs . 10 . 5 . 943–54 . 2001 . 11322868 . 10.1517/13543784.10.5.943 . 39820875 .
4. Parthasarathy HK, MacDonald TM . Mineralocorticoid receptor antagonists . Curr. Hypertens. Rep. . 9 . 1 . 45–52 . 2007 . 17362671 . 10.1007/s11906-007-0009-3. 2090391 .
5. Yang J, Young MJ . Mineralocorticoid receptor antagonists-pharmacodynamics and pharmacokinetic differences . Curr Opin Pharmacol . 27 . 78–85 . 2016 . 26939027 . 10.1016/j.coph.2016.02.005 .
6. Doggrell SA, Brown L . The spironolactone renaissance . Expert Opin Investig Drugs . 10 . 5 . 943–54 . 2001 . 11322868 . 10.1517/13543784.10.5.943 . 39820875 .
7. Sica DA . Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis . Heart Fail Rev . 10 . 1 . 23–9 . 2005 . 15947888 . 10.1007/s10741-005-2345-1 . 21437788 .
8. Maron BA, Leopold JA . Mineralocorticoid receptor antagonists and endothelial function . Curr Opin Investig Drugs . 9 . 9 . 963–9 . 2008 . 18729003 . 2967484 .
9. Book: Oxford Textbook of Medicine: Vol. 1. 2003. Oxford University Press. 978-0-19-262922-7. 1–.
10. Wang S, Rijk JC, Riethoff-Poortman JH, Van Kuijk S, Peijnenburg AA, Bovee TF . Bovine liver slices combined with an androgen transcriptional activation assay: an in-vitro model to study the metabolism and bioactivity of steroids . Anal Bioanal Chem . 397 . 2 . 631–41 . 2010 . 20237917 . 2855805 . 10.1007/s00216-010-3605-z .