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| Trade names | Enol-Luteovis |
| Other names | W-3399; Progesterone 3-cyclopentyl enol ether; PCPE; 3-Cyclopentyloxypregna-3,5-dien-20-one |
| Routes of administration | By mouth |
| Drug class | Progestogen;Progestin;Progestogen ether;Neurosteroid |
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| Chemical and physical data | |
| Formula | C26H38O2 |
| Molar mass | 382.588 g·mol−1 |
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Quingestrone, also known asprogesterone 3-cyclopentyl enol ether (PCPE) and sold under the brand nameEnol-Luteovis, is aprogestin medication which was previously used inbirth control pills inItaly but is now no longer marketed.[1][2][3][4][5] It is takenby mouth.[6]
Quingestrone is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[1][7][8] It has weakglucocorticoid activity.[9][10][11]
Quingestrone was introduced for medical use by 1962.[6][12] It is no longer available.[13]
Quingestrone was formerly used in combination withethinylestradiol ormestranol incombinedbirth control pills inItaly.[2][3] The medication was studied in the clinical prevention ofmiscarriage duringpregnancy, but insufficient efficacy was observed at the dosage assessed (100 mg/day orally).[14][15][16][17]
Along with theretroprogesterone derivativedydrogesterone, quingestrone has been described as a "true" progesterone derivative orprogestogen due to its close similarity to natural progesterone.[18][12] Similarly to progesterone, dydrogesterone, andhydroxyprogesterone caproate, quingestrone is a pure progestogen and lacks anyandrogenic effects.[19] As such, it poses no risk of androgenicside effects orvirilizingteratogenic effects on female fetuses.[19] Quingestrone is said to influence thehypothalamic–pituitary–adrenal axis similarly toprogesterone andmedroxyprogesterone acetate, producingadrenal suppression at sufficiently high doses, and this suggests that it possesses weakglucocorticoid activity similarly to progesterone.[9][10][11]
Quingestrone is a very weak progestogen.[8][11] When administeredorally orintraperitoneally in animals, the medication showed 1/80 and 1/20 the potency ofsubcutaneously injected progesterone, respectively.[8] Similarly, oral doses of quingestrone of 10 to 20 times those of subcutaneous progesterone were insufficient to maintainpregnancy in animals, and oral or intraperitoneal doses of quingestrone 20 to 40 times those of oral or intraperitoneal progesterone were unable to potentiatehexobarbital-inducedanesthesia in animals (which progesterone does and is thought to do by inhibiting thehepaticmetabolism ofbarbiturates).[8] With oral administration of equal doses of progesterone and quingestrone in animals, 3 to 4 times lesspregnanediol was recovered fromurine with quingestrone.[8] The fact that quingestrone is more potent by intraperitoneal than oral administration in animals suggests that it is transformed into a less activemetabolite in theintestines.[8]
The effective dosage of quingestrone in themenstrual delay test has been studied.[20]
Quingestrone has noanesthetic effect in animals, in contrast to progesterone.[21][22]
Quingestrone has been suggested to act as aprodrug of progesterone via slowhydrolysis in the body.[14][23] Indeed, it produces similarmetabolites (e.g.,pregnanediols andallopregnanediols) as progesterone,[14][24] although with differing ratios,[25][4] and notably is the only progestin that is known to produce pregnanediol as a metabolite.[6] Subsequent research has cast doubt on the notion that quingestrone is a prodrug of progesterone however, and indicates that it instead is directlymetabolized into pregnanediols withoutintermediate conversion into progesterone.[8] Based on itschemical structure, quingestrone may be transformed into3α-dihydroprogesterone and/or3β-dihydroprogesterone and then further metabolized intopregnanolones and pregnanediols. 3β-Dihydroprogesterone has been reported to possess about the sameprogestogenicpotency asprogesterone in theClauberg test, whereas 3α-dihydroprogesterone was not assessed.[26][27]
Relative to progesterone, quingestrone shows improvedpharmacokinetics, including higherpotency,[25]oral activity,[28] and a longerterminal half-life and henceduration of action.[23] This is considered to be due to its higherlipophilicity,[23] being stored into and slowly released fromfat.[5][14] Quingestrone also shows slowermetabolism and more stable blood levels, with a longer time to peak concentrations and a less intense peak compared to progesterone.[7] Thebioavailability of quingestrone is highest when it is given as asesame seed oil solution (compared to an oil suspension (~2-fold less) ormicronization (~7-fold less)).[24]
The C3 enol ethers of progesterone are less suited for use viadepot injection relative toprogestogen esters likehydroxyprogesterone caproate due to their susceptibility tooxidativemetabolism.[29]
Thepharmacokinetics of quingestrone have been reviewed.[21]
Quingestrone, also known as progesterone 3-cyclopentyl enol ether (PCPE) or as 3-cyclopentyloxypregna-3,5-dien-20-one, is asyntheticpregnanesteroid and aderivative ofprogesterone.[1] It is specifically the 3-cyclopentylenol ether of progesterone.[1] Quingestrone is closely related toprogesterone 3-acetyl enol ether andpentagestrone acetate (17α-acetoxyprogesterone 3-cyclopentyl enol ether).[1]
Chemical syntheses of quingestrone have been published.[21]
Quingestrone appears to have been firstsynthesized in 1936.[30] It was introduced for medical use inItaly by 1962.[6][12]
Quingestrone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andUSANTooltip United States Adopted Name.[1] It is also known by its developmental code nameW-3399.[1]
Quingestrone was marketed under the brand name Enol-Luteovis.[1][13]
Quingestrone is no longer marketed and hence is no longer available in any country.[13] It was previously available inItaly.[13]
She had been taking an oral contraceptive combining ethinylestradiol and quingestrone since 1980.
Enol Luteovis (3 cyclo-pentyl enol ether of progesterone) is the only oral progestin producing pregnanediol as a metabolite. It is not very potent and probably carries very little risk of producing virilizing effects on a female foetus. Thus it is more closely related to progesterone than the other synthetic progestins.
An interesting substance which has received little attention is the 3-cyclopentyl enol ether of progesterone (quingestrone). It is a very weak progestational agent, requiring 50 mg. per rat for pregnancy maintenance. 100 At this dose quingestrone reduced adrenal weight in male rats to the level observed after hypophysectomy and prevented any rise in plasma corticosteroids in response to a maximally stimulating dose of ACTH.H5 This strongly suggests a direct adrenal effect although the substance may in addition suppress ACTH secretion. It is doubtful, however, that progestational agents have clinically important effects on the human adrenal in the doses conventionally used. Nevertheless, in view of the prolonged exposure of women to gestogens for contraception, this factor deserves continued surveillance.
Dr. Appleby would be doing a scientific service if he extended his trial using [...] preferably, a true progesterone derivative, such as [...] progesterone cyclopentyl enol ether ('Enol Luteovis', Vister).
In the Clauberg bioassay the 3β-hydroxy-4-pregnen-20-one shows about the same potency as progesterone (34). In regard to the biological activity of the 3α epimer no data are available.
Among a large no. of pregnane derivs. the esters of 17-α-hydroxyprogesterone (I), itself of weak lutein hormone action, have a strong and long-lasting gestagen action. The optimal results are obtained with I caproate. It permits the administration of depot doses in clear solns. Within the range of dosage used no androgenic effect was noted. It has no influence on growth and on the secondary sex characteristics in infantile and adult castrate male rats. The 3-enol esters of progesterone, which have a somewhat prolonged action, are less suited for depot administration because of their oxidizability.
