6β-Hydroxy-7α-thiomethylspironolactone

6β-Hydroxy-7α-thiomethylspironolactone
Clinical data
Other names6β-OH-7α-TMS; 6β,17α-Dihydroxy-7α-(methylthio)-3-oxo-pregn-4-ene-21-carboxylic acid γ-lactone
Drug classAntimineralocorticoid
Identifiers
IUPAC name
  • (6S,7S,8R,10R,13S,14S,17R)-6-hydroxy-10,13-dimethyl-7-methylsulfanylspiro[2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-17,5'-oxolane]-2',3-dione
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC23H32O4S
Molar mass404.57 g·mol−1
3D model (JSmol)
SMILES
  • CS[C@@H]1[C@@H](O)C2=CC(=O)CC[C@]2(C)[C@H]3CC[C@@]4(C)[C@@H](CC[C@@]45CCC(=O)O5)[C@H]13
InChI
  • InChI=1S/C23H32O4S/c1-21-8-4-13(24)12-16(21)19(26)20(28-3)18-14(21)5-9-22(2)15(18)6-10-23(22)11-7-17(25)27-23/h12,14-15,18-20,26H,4-11H2,1-3H3/t14-,15-,18+,19-,20-,21+,22-,23+/m0/s1
  • Key:NWLBSWATTSRBOV-DFSNYPBXSA-N

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 100 mg/day spironolactone and its metabolites
CompoundCmax (day 1)Cmax (day 15)AUC (day 15)t1/2
Spironolactone72 ng/mL (173 nmol/L)80 ng/mL (192 nmol/L)231 ng•hour/mL (555 nmol•hour/L)1.4 hours
Canrenone155 ng/mL (455 nmol/L)181 ng/mL (532 nmol/L)2,173 ng•hour/mL (6,382 nmol•hour/L)16.5 hours
7α-TMS359 ng/mL (924 nmol/L)391 ng/mL (1,006 nmol/L)2,804 ng•hour/mL (7,216 nmol•hour/L)13.8 hours
6β-OH-7α-TMS101 ng/mL (250 nmol/L)125 ng/mL (309 nmol/L)1,727 ng•hour/mL (4,269 nmol•hour/L)15.0 hours
Sources: See template.

6β-Hydroxytestosterone, which is analogous to 6β-OH-7α-TMS, has been found to possess virtually no androgenicity.[8]

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. S2CID 39820875.
  4. ↑ Parthasarathy HK, MacDonald TM (2007). "Mineralocorticoid receptor antagonists". Curr. Hypertens. Rep. 9 (1): 45–52. doi:10.1007/s11906-007-0009-3. PMID 17362671. S2CID 2090391.
  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. S2CID 21437788.
  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. ↑ 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. doi:10.1002/j.1552-4604.1989.tb03339.x. PMID 2723123. S2CID 29457093.


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