Trimethyltrienolone (TMT), also known by its developmental code name R-2956 or RU-2956, is an
antiandrogen medication which was never introduced for medical use but has been used in
scientific research.[1][2][3]
Side effects
Due to its close relation to
metribolone (methyltrienolone), it is thought that TMT may produce
hepatotoxicity.[4]
Notes: Values are percentages (%). Reference
ligands (100%) were
progesterone for the
PRTooltip progesterone receptor,
testosterone for the
ARTooltip androgen receptor,
E2 for the
ERTooltip estrogen receptor,
DEXATooltip dexamethasone for the
GRTooltip glucocorticoid receptor, and
aldosterone for the
MRTooltip mineralocorticoid receptor. Sources:[10][11][12][13][6]
TMT was developed by
Roussel Uclaf in
France and was first known as early as 1969.[3][16][15] It was one of the earliest antiandrogens to be discovered and developed, along with others such as
benorterone,
BOMT,
cyproterone, and
cyproterone acetate.[5][17][18][19][20] The drug was under investigation by Roussel Uclaf for potential medical use, but was abandoned in favor of
nonsteroidal antiandrogens like
flutamide and
nilutamide due to their comparative advantage of a complete lack of androgenicity.[1] Roussel Uclaf subsequently developed and introduced nilutamide for medical use.[21]
References
^
abRaynaud JP, Bonne C, Moguilewsky M, Lefebvre FA, Bélanger A, Labrie F (1984). "The pure antiandrogen RU 23908 (Anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer: a review". The Prostate. 5 (3): 299–311.
doi:
10.1002/pros.2990050307.
PMID6374639.
S2CID85417869. [...] flutamide but we soon abandoned the development of steroid derivatives such as RU 2956 because of inherent androgenicity [17], and focused on the nonsteroidal antiandrogens.
^
abRaynaud JP, Ojasoo T (November 1986). "The design and use of sex-steroid antagonists". Journal of Steroid Biochemistry. 25 (5B): 811–833.
doi:
10.1016/0022-4731(86)90313-4.
PMID3543501.
^
abcAzadian-Boulanger G, Bonne C, Secchi J, Raynaud JP (1974).
"[17beta-hydroxy-2,2,17-trimethyl-estra-4, 9,11-trien-3-one). 1. Profil endocrinien. (Antiandrogenic activity of R2956 (17beta-hydroxy-2,2,17-trimethyl-estra-4,9,11-trien-3-one). 1. Endocrine profile)] Activite anti-androgene du R 2956". Journal de Pharmacologie (in French). 5 (4): 509–520. Retrieved 12 August 2016. R 2956 (17beta-hydroxy-2,2,17-trimethyl-estra-4,9,11-trien-3-one) was tested for antiandrogenic activity in rats (Dorfman test); in dogs; for androgenic activity in female rats (Hershberger); in male rats; for progestagenic activity in rabbits (Clauberg); for uterotrophic activity in mice (Rubin); and for antiestrogenic activity in mice (Dorfman). R 2956 significantly antagonized the hypertrophic effect of .05 mg testosterone propionate on rat seminal vesicles and ventral prostate in proportion to dose from .4-5 mg/day orally. In dogs R 2956 lowered prostate epithelial hyperplasia induced by androstanolone. R 2956 had no androgenic, estrogenic, progestational, or antiestrogenic activities and inhibited development of corpora lutea to an extent comparable with that of norethindrone.
^Ostgaard K, Wibe E, Eik-Nes KB (August 1981). "Steroid responsiveness of the human cell line NHIK 3025". Acta Endocrinologica. 97 (4): 551–558.
doi:
10.1530/acta.0.0970551.
PMID7270009.
^Eil C, Douglass EC, Rosenburg SM, Kano-Sueoka T (January 1981). "Receptor characteristics of the rat mammary carcinoma cell line 64-24". Cancer Research. 41 (1): 42–48.
PMID6256064.
^Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, et al. (January 1980). "Steroid hormone receptors and pharmacology". Journal of Steroid Biochemistry. 12: 143–157.
doi:
10.1016/0022-4731(80)90264-2.
PMID7421203.
^Kohtz AS, Frye CA (2012). "Dissociating behavioral, autonomic, and neuroendocrine effects of androgen steroids in animal models". Psychiatric Disorders. Methods in Molecular Biology. Vol. 829. pp. 397–431.
doi:
10.1007/978-1-61779-458-2_26.
ISBN978-1-61779-457-5.
PMID22231829. Administration of steroidal, blocking agents such as spironolactone, cyproterone acetate, or trimethyltrienolone, or nonsteroidal, such as flutamide, bicalutamide, blocking agents, can attain this result (169–171).
^Bratoeff E, Ramírez E, Murillo E, Flores G, Cabeza M (December 1999). "Steroidal antiandrogens and 5alpha-reductase inhibitors". Current Medicinal Chemistry. 6 (12): 1107–23.
doi:
10.2174/0929867306666220401180500.
PMID10519917.
S2CID248057720. Several androstane derivatives have also demonstrated an antiandrogenic activity; 17a-methyl-B-nortestosterone 8 was prepared and tested in 1964 for antihormonal activity [43]. Within the next decade, several other androstane analogs were prepared and found to possess antiandrogenic activity [43, 44, 45, 46] including BOMT 9 "figure 2", R2956 10, SC9420 11, and oxendolone 12 "figure 3".