59122-46-2 Usage
Description
Misoprostol, also known as (16-(R,S)-methyl-16-hydroxy)-PGE1, methyl ester (Cytotec), is a synthetic prostaglandin E1 analog that exhibits potent gastric antisecretory and gastroprotective effects when administered orally. It is a yellow, viscous liquid with a musty odor, miscible with ethanol, ether, or chloroform, and extremely insoluble in water or n-hexane. Misoprostol is sensitive to temperature and pH value changes, undergoing thermal epimerization and isomerization. It is relatively stable in the dispersion system of hydroxypropyl methylcellulose and can be stored at room temperature. Misoprostol is commonly used for medical abortion, management of miscarriage, cervical priming, management of postpartum hemorrhage, and induction of labor. It is listed in the World Health Organization (WHO) Model List of Essential Medicines due to its wide use in reproductive health.
Uses
1. Inducing Labor:
Misoprostol is used as an effective and safe method for inducing labor, particularly in cases where the FDA has not yet approved its use in pregnancy. It acts by causing uterine ripening and contractions of the cervix.
2. Abortion:
Misoprostol is used in combination with other drugs, such as methotrexate or mifepristone, for medical abortion. It works by softening the cervix, causing it to open, and inducing uterine muscle contractions to expel the fetus. It is most effective when administered after 12 weeks of pregnancy and can be used vaginally or orally in the first trimester.
3. Postpartum Hemorrhage:
Misoprostol is used both as treatment and prevention of postpartum hemorrhage due to its uterotonic properties. Although less effective than oxytocin when administered orally, it plays a vital role in treating postpartum hemorrhage when other agents fail or are not available.
4. Prevention of Ulcer:
Misoprostol is commonly used for the treatment and prevention of NSAID-induced gastric and duodenal ulcers due to its analgesic and anti-inflammatory properties. It inhibits gastric acid secretion by decreasing proton pump activity and intracellular cyclic AMP levels at the apical surface of the parietal cell.
5. Failed Miscarriage:
Misoprostol is used in treating a mother in case of fetal death that can result in miscarriage or in the termination of pregnancy for fetal anomalies. It is administered in low doses, with the dosage doubled for extra doses until delivery.
6. Drug Delivery Systems:
Misoprostol can be used in various drug delivery systems, such as organic and metallic nanoparticles, to enhance its applications and efficacy against cancer cells. These systems aim to improve the drug's delivery, bioavailability, and therapeutic outcomes.
7. Gastric Cytoprotective:
Misoprostol may prove useful as a gastric cytoprotective when administered concurrently with irritating drugs, such as nonsteroidal anti-inflammatory drugs.
Brand Names:
Cytotec (Searle), Cyprostol, Oxaprost, Prostalgin.
Pharmacokinetics
Routes for administering misoprostol include orally, sublingually, vaginally, rectally, or buccally. Pharmacokinetics studies carried out to compare vagina and oral administration have revealed that vaginal misoprostol is linked to slower clearance, lower peak plasma levels, and slower absorption, similar to an extended release preparation. Conversely, vaginal misoprostol is associated with more significant effects on the uterus and cervix due to the higher overall exposure to the drug.
Administration through the rectum revealed a similar pattern to vaginal administration; however, it has lower AUC and lower maximum peak concentration. The sublingual route has higher peak levels and more rapid absorption as compared to oral or vaginal administration.
Adverse Drug Reactions
The general adverse reactions experienced include contractions, abdominal pain, and GI intolerance and diarrhea. Many clinical studies revealed that about 13% of patients experienced diarrhea in the initial stages of therapy.
The most often reported side effects of orally taking the drug for the prevention and treatment of gastric ulcers include nausea, abdominal pain, headache, flatulence, dyspepsia, constipation, nausea, and constipation. Many patients experience fever when given multiple doses every 4 to 6 hours.
Women with wanted pregnancies are not supposed to take misoprostol to reduce the risk of increased uterine contractions and tone due to NSAID-induced gastric ulcers. This may cause complete or partial abortions or may lead to pregnancies with linked to congenital disabilities.
The drug may cause uterine hyperstimulation, which can affect the blood supply to the uterus negatively, thus increasing the chances of developing complications such as rupture of the womb.
Controversy
There have been numerous controversies regarding the use of misoprostol for induction of labor due to various reasons. The use of misoprostol and mifepristone for medical abortion has the potential of improving access to abortion services; therefore, political opponents of abortion may view the drugs as a target and a threat. It is noteworthy that in 2000, the FDA approved the use of mifepristone and misoprostol in conjunction with misoprostol for the termination of early pregnancy, yet misoprostol was not approved for the same purpose.
Originator
Searle (USA)
Indications
Misoprostol (Cytotec), which is an analogue of
prostaglandin E1, has been approved for use in the prevention
of nonsteroidal antiinflammatory drug–induced
ulceration. It also is approved in other countries for the
treatment of peptic ulcer disease.
Preparation
synthesis of MisoprostolTo a 1000 ml dried flask under a nitrogen atmosphere was added 74.6 g of(E)-trimethyl-[[1-methyl-1-[3-(tributylstannyl)-2-propenyl]pentyl]oxy]silane,125 ml anhydrous THF and 24.2 g of copper (I) iodide. The mixture wasstirred at room temperature for 30 minutes and then it was cooled to -25 to -30°C. 98.8 ml of methyllithium (2.86 M) in DEM was added dropwise and theresultant solution was stirred at -15°C for 2 hours. Then the reaction mixturewas cooled to -78°C and 25 g of methyl-5-oxo-3-[(triethylsilyl)oxy]-1-cyclopentene-1-heptanoate in 100 ml of THF was added rapidly. After stirringthe mixture for 5 min at -78°C, it was quenched into a mixture of 750 ml ofaqueous ammonium chloride solution and 200 ml of ammonium hydroxide.The resulting mixture was warmed to room temperature and stirred until adeep blue aqueous layer was obtained. Ethyl acetate (250 ml) was used forextraction. Then the combined organic layers were washed with brine andsubsequently dried over magnesium sulfate. After a filtration andconcentration under reduced pressure, an oil (105 g) was obtained. This oilcontaining the protected prostaglandin was subjected to acidic deprotection(cat. PPTS, acetone and water) and purification (chromatography on silica gel)to provide 15.8 g (60%) of misoprostol was identical.
Therapeutic Function
Antiulcer
Biological Activity
Cytoprotective prostaglandin E 1 analog that displays agonist activity at EP receptors. K i values are 120, 250, 67 and 67 nM at cloned mouse EP 1 , EP 2 , EP 3 and EP 4 receptors respectively. Prevents NSAID-induced gastric ulceration.
Pharmacology
Misoprostol is absorbed
rapidly after oral administration and is hydrolyzed
to the active compound. It is metabolized by
the liver and excreted mainly in the urine. Adverse effects
include crampy abdominal pain, dose-related diarrhea,
and uterine contractions. The last-named effect
has led to its use in the control of postpartum bleeding.
Clinical Use
Benign gastric and duodenal ulceration and NSAID
associated ulceration
Prophylaxis of NSAID induced ulceration
Veterinary Drugs and Treatments
Misoprostol may be useful as primary or adjunctive therapy in
treating or preventing
gastric ulceration, especially when caused
or aggravated by non-steroidal antiinflammatory drugs (NSAIDs).
Misoprostol is most useful to prevent GI ulceration or GI adverse
effects (anorexia, vomiting) associated with NSAID therapy. While
it can be used for treating gastric ulcers, other drugs are probably
just as effective and less expensive. It does not appear to be very
effective in reducing gastric ulceration secondary to high dose corticosteroid
therapy
Misoprostol may be efficacious in reducing or reversing cyclosporine-
induced nephrotoxicity. More data is needed to confirm
this effect.
One study demonstrated that misoprostol can reduce the clinical
signs associated with atopy somewhat in dogs.
Misoprostol’s effects on uterine contractibility and cervical softening/
opening make it effective as an adjunctive treatment in pregnancy
termination.
Metabolism
Rapidly metabolised to its active form (misoprostol acid)
after oral doses. Misoprostol acid is further metabolised
by oxidation in several body organs and is excreted mainly
in the urine.
Mode of action
Misoprostol is a synthetic prostaglandin E1 analogue which has ulcer healing, gastric acid antisecretory and mucosal protective properties. The antisecretory activity is mediated by direct action on specific prostaglandin receptors on the surface of gastric parietal cells. In dogs with innervated Pavlov pouches, inhibition of secretion is achieved at a lower dosage by intrapouch injection than by intravenous or intragastric administration, suggesting that the local effect may predominate. The mucosal protective effect against various damaging agents has been demonstrated in humans with doses that inhibit and doses which minimally affect acid secretion.
Check Digit Verification of cas no
The CAS Registry Mumber 59122-46-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,9,1,2 and 2 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 59122-46:
(7*5)+(6*9)+(5*1)+(4*2)+(3*2)+(2*4)+(1*6)=122
122 % 10 = 2
So 59122-46-2 is a valid CAS Registry Number.
InChI:InChI=1/C23H40O4/c1-5-6-15-23(2,3)16-11-13-19-18(20(24)17-21(19)25)12-9-7-8-10-14-22(26)27-4/h11,13,18-19,21,25H,5-10,12,14-17H2,1-4H3/b13-11+/t18-,19-,21-/m1/s1
59122-46-2Relevant articles and documents
-
Collins,P.W. et al.
, p. 3187 - 3190 (1978)
-
Prostanoids: Synthesis of enantiomers of 15-deoxy-16-hydroxy-16-methylprostaglandin E1
Terinek, Miroslav,Kozmik, Vaclav,Palecek, Jaroslav
, p. 1325 - 1341 (2007/10/03)
Four optically pure isomers of methyl 11,16-dihydroxy-16-methyl-9-oxoprost-13-enoate (1a-1d) were synthesized using an approach reverse to the classical Corey procedure, the key intermediates being the easily accessible (-)- and (+)-enantiomers of the Corey lactone, 2a and 2b.
In Situ Cuprate Formation via Transmetalation between Vinylstannanes and Higher Order Cyanocuprates
Behling, James R.,Babiak, Kevin A.,Ng, John S.,Campbell, Arthur L.,Moretti, Robert,et al.
, p. 2641 - 2643 (2007/10/02)
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