Alprostadil

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

Alprostadil 2 A1restatin 3, 72 Althiazide T, 359 Alverine 2, 55 Amacetam 7, 127 Amantidine 2 18 Ambucaine 11... 

Intracavernosal Alprostadil Caverject, Caverject Impulse, Edex 1.25-60 meg 5-20 minutes prior to intercourse0 Three times weekly, 24 hours between injections... 

Intraurethral Alprostadil MUSE 125-1000 meg 5-10 minutes prior to intercourse0 Two times daily... 

Alprostadil is a prostaglandin E, analog that induces an erection by stimulating adenyl cyclase, which leads to an increase... 

Alprostadil injected into the corpus cavernosum is the more effective form and is the only Food and Drug Administration (FDA)-approved agent for injection. The onset of action is... 

Pco2—partial pressure (tension) of carbon dioxide, artery PDGP—pi ate let-derived growth factor PGEi—prostaglandin Ei (alprostadil)... 

Intraurethral Alprostadil (MUSE) 125-mcg 250-mcg 500-mcg 1,000-mcg pellet 125-1,000 meg 5-10 minutes before intercourse... 

Papaverine 30 mg/mL injection Variable, usually used in combination with alprostadil and phentolamine... 

VEDs can be used as second-line therapy after failure of oral or injectable drugs. Adding alprostadil to a VED improves the response rate. 

Alprostadil, or prostaglandin E1 stimulates adenyl cyclase to increase production of cyclic adenosine monophosphate, a neurotransmitter that ultimately enhances blood flow to and blood filling of the corpora. 

Alprostadil is approved as monotherapy for the management of ED. It is generally prescribed after failure of VEDs and phosphodiesterase inhibitors and for patients who cannot use these therapies. Of the available routes, the intracavern os al route is preferred over the intraurethral route because of better efficacy. 

Intracavernosal alprostadil is effective in 70% to 90% ofpatients. However, a high proportion of patients discontinue its use because of perceived ineffectiveness inconvenience of administration unnatural, nonspontane-ous erection needle phobia loss of interest and cost of therapy. 

Intracavernosal alprostadil has been used successfully in combination with VEDs or vasoactive agents (e.g., papaverine, phentolamine, atropine) that act by different mechanisms. Phosphodiesterase inhibitors should not be added to intracavernosal alprostadil because the combination can cause prolonged erections and priapism. 

Intracavernosal alprostadil acts rapidly with an onset of 5 to 15 minutes. The duration of action is dose related and, within the usual dosage range, lasts less than 1 hour. 

The usual dose of intracavernosal alprostadil is 10 to 20 meg up to a maximum of 60 meg. Patients should start with 1.25 meg, which should be increased by 1.25 to 2.50 meg at 30-minute intervals to the lowest dose that produces a firm erection for 1 hour and does not produce adverse effects. In clinical practice, however, most patients start with 10 meg and titrate quickly. 

Intracavernosal alprostadil should be injected 5 to 10 minutes before intercourse using a 0.5-inch, 27- or 30-gauge needle or an autoinjector. The maximum number of injections is one per day and three per week. 

Intracavernosal alprostadil is most commonly associated with local adverse effects, usually during the first year of therapy. Adverse events include... 

Intraurethral alprostadil, 125 to 1,000 meg, should be administered 5 to 10 minutes before intercourse. Before administration, the patient should empty his bladder and void completely. No more than two doses per day are recommended. 

Female partners may experience vaginal burning, itching, or pain, which is probably related to transfer of alprostadil from the man s urethra to the women s vagina during intercourse. 

Matson, M. T., Ramstad, T., and Dunn, M. J. (2005). Purity determination of alprostadil by micellar electrokinetic chromatography with signal enhancement involving field-amplified sample stacking and extended path length detection. /. Liq. Chromatogr. Relat. Technol. 28, 3181—3203. 

A conveniently short synthesis of alprostadil begins with a mixed aldol assembly of the requisite cyclopentenone 13. This product is then oxidatively cleaved with periodate-permanganate and the alcohol moiety is protected as the tetra-hydropyranyl ether (14). Aqueous chromous sulfate satisfactorily reduces the olefinic linkage and the trans stereoisomer 15 predominates after work-up. The remainder of the synthesis of involves the usual steps, through to with the exception that thexyl tetrahydrolimonyllithium borohydride is used to reduce the C-15 keto moiety so as to produce preferentially the desired C-15 stereochemistry. 

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