Hydroxyprogesterone heptanoate
Chemical compound
Hydroxyprogesterone heptanoate Trade names H.O.P, Hydroxyprogesterone, Lutogil A.P., Lutogyl A.P., others Other names OHPH; Hydroxyprogesterone enanthate; OHPE; 17α-Hydroxyprogesterone heptanoate; 17α-Hydroxyprogesterone heptylate; 17α-Hydroxypregn-4-ene-3,20-dione 17α-heptanoate; 17α-Heptyloylpregn-4-ene-3,20-dione Routes of administration Intramuscular injection Drug class Progestogen ; Progestin ; Progestogen ester ATC code
[(8R ,9S ,10R ,13S ,14S ,17R )-17-Acetyl-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H -cyclopenta[a ]phenanthren-17-yl] heptanoate
CAS Number PubChem CID ChemSpider UNII CompTox Dashboard (EPA ) ECHA InfoCard 100.022.724 Formula C 28 H 42 O 4 Molar mass 442.640 g·mol−1 3D model (JSmol )
CCCCCCC(=O)OC1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C)C(=O)C
InChI=1S/C28H42O4/c1-5-6-7-8-9-25(31)32-28(19(2)29)17-14-24-22-11-10-20-18-21(30)12-15-26(20,3)23(22)13-16-27(24,28)4/h18,22-24H,5-17H2,1-4H3/t22-,23+,24+,26+,27+,28+/m1/s1
Key:NKJYZYWCGKSMSV-BDPSOKNUSA-N
Hydroxyprogesterone heptanoate (OHPH ), also known as hydroxyprogesterone enanthate (OHPE ) and sold under the brand names H.O.P. , Lutogil A.P. , and Lutogyl A.P. among others, is a progestin medication used for progestogenic indications.[1] [2] [3] [4] It has been formulated both alone and in together with estrogens , androgens /anabolic steroids , and other progestogens in several combination preparations (brand names Tocogestan , Trioestrine Retard , and Triormon Depositum ).[4] [5] [6] [7] [8] [9] [10] OHPH is given by injection into muscle at regular intervals.[11] [9]
OHPH is a progestin, or a synthetic progestogen , and hence is an agonist of the progesterone receptor , the biological target of progestogens like progesterone .[12] [13] [14] It appears to have similar pharmacology to that of the closely related medication hydroxyprogesterone caproate (OHPC).[15] [16] [17]
OHPH was first described by 1954[16] and was introduced for medical use by 1957.[6] It has been used clinically in France and Monaco in the past but is no longer marketed.[2] [3] [4]
Medical uses
OHPH is a progestogen and was used in situations in which progestogens were indicated.[12] [13] [14]
OHPH was provided as a 125 mg/1 mL oil solution for use by intramuscular injection .[3] [11] In addition to single-drug preparations, OHPH has also been used in a number of multi-drug formulations.[4] [5] [6] [7] [8] [9] [10] It was used in Tocogestan , a combination of 50 mg progesterone , 200 mg OHPH, and 250 mg α-tocopherol palmitate (vitamin E ) in oil solution for use by intramuscular injection.[18] [4] [5] It was also used in Triormon Depositum (estradiol dibutyrate , testosterone caproate , and OHPH) and Trioestrine Retard (estradiol diundecylate , testosterone cyclohexylpropionate , and OHPH).[6] [7] OHPH was a component of the experimental preparation Trophobolene (or Trophoboline), which also contained estrapronicate (estradiol nicotinate propionate) and nandrolone undecanoate , as well.[8] [9] [10]
Pharmacology
Pharmacodynamics
OHPH is a progestin, or a synthetic progestogen , and hence is an agonist of the progesterone receptor , the biological target of progestogens like progesterone .[15] [12] [13] [14] The progestogenic potency of OHPH in the uterus is equal to or greater than that of progesterone when administered by subcutaneous injection in animals.[15] [16] [17] Its potency in animals likewise appears to be similar to that of hydroxyprogesterone caproate .[15] [16] [17]
Pharmacokinetics
OHPH shows a pronounced depot effect when administered by subcutaneous injection in animals, similarly to the closely related medication hydroxyprogesterone caproate .[15] [16] The oral activity of OHPH in animals does not appear to have been assessed.[15]
Chemistry
OHPH, also known as hydroxyprogesterone enanthate (OHPE),[19] as well as 17α-hydroxyprogesterone heptanoate or 17α-hydroxypregn-4-ene-3,20-dione 17α-heptanoate, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone .[1] [2] It is a progestogen ester ; specifically, it is the C17α heptanoate (enanthate) ester of 17α-hydroxyprogesterone.[1] [2] Analogues of OHPH include the more well-known medications hydroxyprogesterone acetate and hydroxyprogesterone caproate (hydroxyprogesterone hexanoate).[1] [2] The C3 benzilic acid hydrazone of OHPH, hydroxyprogesterone heptanoate benzilic acid hydrazone (OHPHBH), is known and has been studied in animals.[20] [21] In terms of chemical structure , OHPH is very similar to hydroxyprogesterone caproate, differing from it only in having one additional carbon in its fatty acid ester chain .[1] [2]
History
OHPH was first described, along with hydroxyprogesterone caproate and hydroxyprogesterone acetate , by Karl Junkmann of Schering AG in 1954.[16] [19] It was introduced for medical use by 1957.[6] OHPH was commercialized by Roussel and Théramex , and has been used clinically in France and Monaco but is no longer marketed.[2] [3] [4]
Society and culture
Brand names
OHPH has been marketed alone under a number of brand names including H.O.P, Hydroxyprogesterone, Lutogil A.P., and Lutogyl A.P.[1] [2] [3] [4]
Availability
OHPH was previously marketed in France and Monaco but is no longer available.[2] [3] [22]
See also
References
^ a b c d e f Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 665–. ISBN 978-1-4757-2085-3 .
^ a b c d e f g h i Index Nominum 2000: International Drug Directory . Taylor & Francis. January 2000. pp. 532–. ISBN 978-3-88763-075-1 .
^ a b c d e f Muller NF, Dessing RP (19 June 1998). European Drug Index: European Drug Registrations (Fourth ed.). CRC Press. pp. 612–. ISBN 978-3-7692-2114-5 .
^ a b c d e f g Kleemann A, Engel J (2001). Pharmaceutical Substances: Syntheses, Patents, Applications . Thieme. p. 1033. ISBN 978-3-13-558404-1 .
^ a b c Sasco AJ, Gendre I, Verbier-Naneix C, Soulier JL, Raffi F, Satgé D, Robert E (1998). "Neonatal neuroblastoma and in utero exposure to progestagens" . International Journal of Risk and Safety in Medicine . 11 (2): 121–128.
^ a b c d e Ermiglia G, Valli P (1957). "Triormon depositum in climacteric syndrome. Curves of excretion of catabolites and duration of the therapeutic effect". Quaderni Clin. Ostet. E Ginecol . 12 : 284–93. Triormon depositum (estradiol dibutyrate 3, testosterone caprylate 50, and hydroxyprogesterone heptanoate 30 mg.), administered in castor oil-benzyl benzoate soln. or polyvinylpyrrolidone suspension to 21 women in climacteric, was followed by estradiol, pregnanediol, and 17-keto steroid urinary curves, most with a peak at the 4th day, and approaching starting values at the 8-10th day. The therapeutic efficacy of the drug was satisfactory.
^ a b c Bordier P (1963). "Cure of fifteen osteoporosis cases by a delayed effect of hormonal association". Semaine des Hopitaux . 39 (2): 81–4. ISSN 0037-1777 . The patients (females) received intramuscularly, every 10 days for 2-3 months, estradiol diundecyleate 2.25, testosterone cyclohexylpropionate 67.5, and hydroxyprogesterone heptylate 100 mg. ("trioestrine retard"). Their av. calcuria decreased 30.5% (0-69%) and asthenia, anorexia, and muscular activity improved.
^ a b c Excerpta medica. Section 8, Neurology and neurosurgery . 1981. p. 10.
^ a b c d "Nandarolone" . Testosterone Congeners—Advances in Research and Application: 2013 Edition: ScholarlyBrief . ScholarlyEditions. 21 June 2013. pp. 137–. ISBN 978-1-4816-9288-5 .
^ a b c Frigerio A (1981). Chromatography in Biochemistry, Medicine and Environmental Research: Proceedings of the ... International Symposium on Chromatography in Biochemistry, Medicine and Environmental Research . Elsevier Scientific Publishing Company. p. 99. ISBN 9780444420169 .
^ a b Krówczyński L (1987). Extended Release Dosage Forms . CRC Press. p. 12. ISBN 978-0-8493-4307-0 . Progestogens. [...] Hydroxyprogesterone heptanoate. Hydroxyprogesterone (Theramex). Oily solution for injection.
^ a b c Schindler AE (July 2014). "The "newer" progestogens and postmenopausal hormone therapy (HRT)". The Journal of Steroid Biochemistry and Molecular Biology . 142 : 48–51. doi :10.1016/j.jsbmb.2013.12.003 . PMID 24333799 . S2CID 32126275 .
^ a b c Bińkowska M, Woroń J (June 2015). "Progestogens in menopausal hormone therapy" . Przeglad Menopauzalny = Menopause Review . 14 (2): 134–143. doi :10.5114/pm.2015.52154 . PMC 4498031 . PMID 26327902 .
^ a b c Posaci C, Smitz J, Camus M, Osmanagaoglu K, Devroey P (June 2000). "Progesterone for the luteal support of assisted reproductive technologies: clinical options" . Human Reproduction . 15 (suppl 1): 129–148. doi :10.1093/humrep/15.suppl_1.129 . PMID 10928425 .
^ a b c d e f Neumann F, Elger W, Salloch RR, Tube O, Neumann HF (1969). "Besonderheiten der Wirkungen der einzelnen Gestagene auf Morphologie und Funktion des Genitaltraktes bei Säugetieren" [Special features of the effects of the individual gestagens on the morphology and function of the genital tract in mammals]. Die Gestagene [Progestogens ]. Vol. 2. Springer-Verlag. pp. 50–131. ISBN 978-3-662-00826-3 .
^ a b c d e f Junkmann K (1954). "Über protrahiert wirksame Gestagene". Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie . 223 (3). doi :10.1007/BF00246995 . S2CID 33591186 .
^ a b c Junkmann K (1959). Über Entwicklungen auf dem Gestagengebiet. 15 . General Assembly of the Japan Medical Congress, Tokyo. Vol. 1. pp. 697–706.
^ "Formulation" .
^ a b Batres E, Gomez R, Rosenkranz G, Sondheimer F (1956). "Notes - Steroids. LXXVI. Synthesis of Long Chain Carboxylic Acid Esters of 17α-Hydroxyprogesterone". The Journal of Organic Chemistry . 21 (2): 240–241. doi :10.1021/jo01108a601 . ISSN 0022-3263 .
^ Shipley EG (1962). "Anti-gonadotropic steroids, inhibition of ovulation and mating" . In Dorfman RI (ed.). Methods in Hormone Research . Vol. 2. Elsevier. pp. 252–. ISBN 978-1-4832-7276-4 .
^ Gleason CH, Parker JM (1959). "The duration of activity of the benziloyl hydrazones of testosterone-17-heptanoate, estrone-3-heptanoate and 17α-hydroxy-progesterone-17-heptanoate". Endocrinology . 65 (3): 508–511. doi :10.1210/endo-65-3-508 . ISSN 0013-7227 . PMID 13828402 .
^ "OHPH" . micromedexsolutions.com .
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