Acetomepregenol Explained

Acetomepregenol (ACM), also known as mepregenol diacetate and sold under the brand name Diamol, is a progestin medication which is used in Russia for the treatment of gynecological conditions and as a method of birth control in combination with an estrogen.^{[1] [2] [3] [4] [5] [6] [7]} It has also been studied in the treatment of threatened abortion. It has been used in veterinary medicine as well.^{[8] [9] [10]} It has been marketed since at least 1981.

Pharmacology

Based on its chemical structure, namely the lack of a C3 ketone, it is probable that acetomepregenol is a prodrug of megestrol acetate (the 3-keto analogue).^{[11] [12]}

Chemistry

See also: List of progestogens, Progestogen ester and List of progestogen esters.

Acetomepregenol, also known as megestrol 3β,17α-diacetate, as well as 3β-dihydro-6-dehydro-6-methyl-17α-hydroxyprogesterone diacetate or as 3β,17α-diacetoxy-6-methylpregna-4,6-dien-20-one, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone. It is very close to megestrol acetate (6-dehydro-6-methyl-17α-acetoxyprogesterone) in structure, except that there is a hydroxyl group with an acetate ester attached at the C3 position instead of a ketone. A closely related medication is cymegesolate (also known as megestrol 3β-cypionate 17α-acetate), which, in contrast, has not been marketed.^{[13] [14]}

Notes and References

1. Korkhov VV . [Current trends in the development of oral contraception] . ru . Farmakologiia I Toksikologiia . 48 . 4 . 119–122 . 1985 . 3899717 .
2. Nikitina GV, Savchenko ON, Stepanov MG . [Hormonal properties of new 17 alpha-hydroxyprogesterone derivatives] . ru . Problemy Endokrinologii . 33 . 3 . 60–63 . 1987 . 3116530 .
3. Sidel'nikova VM, Demidova EM, Borisova I, Dondukova TM, Absava GI, Korkhov VV . [The use of acetomepegrenol in the therapy of threatened abortion] . ru . Akusherstvo I Ginekologiia . 9 . 37–40 . September 1990 . 2278305 .
4. Grinenko GS, Popova EV, Korkhov VV, Lesik EA, Petrosyan MA, Topil'skaya NI . Synthesis and biological activity of 17α-acetoxy-3β-phenylpropionyloxy-6-methylpregna-4,6-dien-20-one. Pharmaceutical Chemistry Journal. 1573-9031. 113–114. 34. 3. March 2000. 10.1007/BF02524577 . 44235508. Note that 3,17-diacetoxy-6-methylpregna-4,6-dien-20-one (1b), a structural analog of compound 1a, is certified in Russia under the trade name acetomepregnol and recommended for therapeutic purposes in gynecological practice and as a contraceptive preparation in combination with estrogens [4]..
5. Mashkovskii MD . Eightieth Anniversary of the Drug Chemistry Center/All-Russian Pharmaceutical Chemistry Scientific Research Institute. Pharmaceutical Chemistry Journal. 1573-9031. 677–680. 34. 12. 10.1023/A:1010416205068. December 2000. 24703856.
6. Sergeev PV, Rzheznikov VM, Korkhov VV, Grinenko GS, Semeikin AV, Mayatskaya EE, Samoilikov RV, Shimanovskii NL . 6 . Investigation of the gestagen activity of 17α-acetoxy-3β-butanoyloxy-6-methylpregna-4, 6-dien-20-one. . Pharmaceutical Chemistry Journal . 39 . 7 . 358–360 . July 2005. 10.1007/s11094-005-0154-4 . 35450212. Gestagens are widely used in medicine as drugs for the treatment of breast and uterine tumors, endometriosis, uterine bleeding, and premenstrual syndrome, as a means of hormonal therapy and maintenance of pregnancy, and as contraceptives [1, 2]. In clinics, drugs of this group are represented by acetomepregenol (AMP), medroxyprogesterone acetate (MPA), levonorgestrel, progesterone, didrogesterone, etc. [1]..
7. Zeinalov OA, Yaderets VV, Stytsenko TS, Petrosyan MA, Andryushina VA . Synthesis and biological activity of synthetic 17α-hydroxyprogesterone derivatives. Pharmaceutical Chemistry Journal. July 2012. 1573-9031. 203–206. 46. 4. 10.1007/s11094-012-0761-9 . 7159432.
8. Bratanov K, Bankov N, Doichev S, Pisheva M, Klinskii IU, Zhirkov G . 1981 . Action of diacetate mepregnol (diamol) on estrus induction in sheep in physiological anestrus. . Reguliatsiia i intensifikatsiia protsessov razmnozheniia sel'skokhoziaistvennykh zhivotnykh: trudy Mezhdunarodnogo simpoziuma, sostoiavshegosia v Sofii, mai 1980 godina/[red. koll.: K. Bratanov (otvet. red.)... i dr.] .
9. Zhirkov GF . 1981 . Testing diamol on sheep on a fattening farm. . Biulleten'nauchnykh Rabot-Vsesoiuznyi Nauchno-issledovatel'skii Institut Zhivotnovodstva .
10. Klinskii I, Zhirkov GF . [Use of mepregenol diacetate (Diamol), a gestagen preparation, for estrus synchronization in caracul sheep during mating season] . ru . Archiv Fur Experimentelle Veterinarmedizin . 36 . 1 . 159–162 . January 1982 . 7201304 .
11. Book: Ian S. Fraser. Estrogens and Progestogens in Clinical Practice. 1998. Churchill Livingstone. 978-0-443-04706-0. 281. Progestational activity depends on the presence of a 3-keto group in ring A of the steroid skeleton. Most of the progestogens used today do indeed carry such a group in their original molecules. However, the 3-keto group is initially missing in the case of desogestrel and norgestimate. They are prodrugs which undergo metabolic conversion to active 3-keto derivatives in the body..
12. McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK . Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay . The Journal of Steroid Biochemistry and Molecular Biology . 110 . 1–2 . 39–47 . May 2008 . 18395441 . 10.1016/j.jsbmb.2007.10.008 . Prodrugs (lack 3-keto): Ethylestrenol, Lynestrenol, Ethynodiol, Allylestrenol, Norgestimate . 5612000 .
13. De-Wei Z . Research activities in the field of oral contraceptives in the People's Republic of China . Acta Obstetricia et Gynecologica Scandinavica. Supplement . 105 . 51–60 . 1982 . 6952745 . 10.3109/00016348209155319 . 44858028 .
14. Book: Yang YC, Gu XG, Li SX . Antifertility Effect of a Long-Acting Progestin (3-Cyclopentyl Propionate of Megestrol Acetate): Prematurity of the Endometrium and Accompanying Changes of Uteroglobin and Progesterone in Uterine Fluid . Proteins and Steroids in Early Pregnancy . 1982. 335–342. 10.1007/978-3-642-67890-5_22. 978-3-642-67892-9.