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Gene & Protein in Disease Diagnosis and treatment of aldosterone-related diseases

Table 1. Comparison of three generations of MRAs
Drug type First generation Second generation Third generation
Representative drug name Spironolactone Eplerenone Finerenone
Molecular structure Steroidal Steroidal Non-steroidal
Selectivity for MR Non-selective Non-selective Selective
Half-life (h) 1.4 4–6 1.7–2.8
IC50 (nM) 24 990 17.8
Usual dosage (mg/d) 25–50 (RHTN) 50–100 (RHTN) 10–20 (hypertension)
Status Listed Listed Listed
Adverse reactions Gynecomastia, irregular Renal insufficiency Increased levels of creatine kinase
menstruation in women, renal and hyperkalemia and blood glucose levels, headache,
insufficiency, and hyperkalemia dizziness
IC , drug concentration required to inhibit 50% of receptor activation; RHTN: Refractory hypertension
50

levels is still increasing and it is difficult to effectively Author contributions
treat the complications associated with these diseases.
Spironolactone, as a non-selective competitive antagonist Conceptualization: Sujuan Wang
with the longest clinical application, can regulate the Writing – original draft: Sujuan Wang
balance of salt and water in the body as well as improve Writing – review & editing: Sujuan Wang, Qiaohui Zhao,
the adverse cardiovascular effects caused by abnormal
ALD levels. However, it is challenging to overcome Tianyun Wang
the hormonal disorders caused by the long-term use Ethics approval and consent to participate
of spironolactone, such as male-female emulsification
and irregular menstruation in women. Therefore, if the Not applicable.
aforementioned adverse reactions occur during treatment,
another antagonist known as eplerenone will be used Consent for publication
in place of spironolactone. Eplerenone is a selective Not applicable.
antagonist that can effectively overcome the adverse
reactions caused by the long-term use of spironolactone. Availability of data
However, it is imperative to address the adverse reactions
including hyperkalemia caused by spironolactone and Not applicable.
eplerenone. Finerenone has shown absolute advantage in References
lowering blood pressure and serum potassium, with some
improvement in diabetes, chronic kidney disease, and 1. Wannachalee T, Turcu AF, 2021, Primary Aldosteronism:
other diseases. Therefore, finerenone, a third-generation A Continuum from Normotension to Hypertension. Curr
antagonist that has been approved for marketing by the Cardiol Rep, 23(8): 105.
FDA, not only plays a role in the treatment of chronic https://doi.org/10.1007/s11886-021-01538-8
kidney disease with Type 2 diabetes, but also has great 2. Knights KM, Winner LK, Elliot DJ, et al., 2009, Aldosterone
potential in the treatment of cardiovascular disease.
glucuronidation by human liver and kidney microsomes
Acknowledgments and recombinant UDP-glucuronosyltransferases: inhibition
by NSAIDs. Br J Clin Pharmacol, 68(3): 402–412.
None.
https://doi.org/10.1111/j.1365-2125.2009.03469.x
Funding 3. Gideon A, Sauter C, Ehlert U, et al., 2021, Aldosterone

This work was supported by the Basic Research Project hyperreactivity to acute psychosocial stress induction in
of Henan Provincial Key Scientific Research Program men with essential hypertension. Horm Behav, 134: 105018.
(No. 20zx013). https://doi.org/10.1016/j.yhbeh.2021.105018
Conflict of interest 4. Ambroisine ML, Milliez P, Nehme J, et al., 2004, Aldosterone
and anti-aldosterone effects in cardiovascular diseases and
The authors declare no conflict of interest. diabetic nephropathy. Diabetes Metab, 30(4): 311–318.

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