6β-Hydroxy-7α-thiomethylspironolactone

6β-Hydroxy-7α-thiomethylspironolactone
Clinical data
Synonyms 6β-OH-7α-TMS; 6β,17α-Dihydroxy-7α-(methylthio)-3-oxo-pregn-4-ene-21-carboxylic acid γ-lactone
Drug class Antimineralocorticoid
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C23H32O4S
Molar mass 404.57 g·mol−1
3D model (JSmol)

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][2][1][3]

Spironolactone is a prodrug with a short terminal half-life of 1.4 hours.[5][6][7] 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.[5][6]

Pharmacokinetics of spironolactone and metabolites[8]
CompoundCmax (ng/mL)
(day 1)
Cmax (ng/mL)
(day 15)
AUC (ng•hr/ml)
(day 15)
t1/2 (hr)
Spironolactone72802311.4
Canrenone155181217316.5
7α-TMS359391280413.8
6β-OH-7α-TMS101125172715.0

6β-Hydroxytestosterone, which is analogous to 6β-OH-7α-TMS, has been found to possess virtually no androgenicity.[9]

See also

References

  1. 1 2 Yang J, Young MJ (2016). "Mineralocorticoid receptor antagonists-pharmacodynamics and pharmacokinetic differences". Curr Opin Pharmacol. 27: 78–85. doi:10.1016/j.coph.2016.02.005. PMID 26939027.
  2. 1 2 Kolkhof P, Bärfacker L (2017). "30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development". J. Endocrinol. 234 (1): T125–T140. doi:10.1530/JOE-16-0600. PMC 5488394. PMID 28634268.
  3. 1 2 Doggrell SA, Brown L (2001). "The spironolactone renaissance". Expert Opin Investig Drugs. 10 (5): 943–54. doi:10.1517/13543784.10.5.943. PMID 11322868.
  4. Parthasarathy HK, MacDonald TM (2007). "Mineralocorticoid receptor antagonists". Curr. Hypertens. Rep. 9 (1): 45–52. PMID 17362671.
  5. 1 2 Sica DA (2005). "Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis". Heart Fail Rev. 10 (1): 23–9. doi:10.1007/s10741-005-2345-1. PMID 15947888.
  6. 1 2 Maron BA, Leopold JA (2008). "Mineralocorticoid receptor antagonists and endothelial function". Curr Opin Investig Drugs. 9 (9): 963–9. PMC 2967484. PMID 18729003.
  7. Oxford Textbook of Medicine: Vol. 1. Oxford University Press. 2003. pp. 1–. ISBN 978-0-19-262922-7.
  8. Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, Stubbs K, Smith M, Karim A (1989). "Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites". J Clin Pharmacol. 29 (4): 342–7. PMID 2723123.
  9. Wang S, Rijk JC, Riethoff-Poortman JH, Van Kuijk S, Peijnenburg AA, Bovee TF (2010). "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. doi:10.1007/s00216-010-3605-z. PMC 2855805. PMID 20237917.

Further reading

  • Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, Stubbs K, Smith M, Karim A (1989). "Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites". J Clin Pharmacol. 29 (4): 342–7. PMID 2723123. 



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