Male erectile dysfunction

FIGURE 48-2. Available devices and prostheses used to treat erectile dysfunction. (From Wagner G, Saenz de Tejada I. Update on male erectile dysfunction. BMJ 1998 316 681, with permission.)... 

Wagner G, Saenz de Tejada I. Update on male erectile dysfunction. BMI 1998 316 678-682. 

Plenty of biological activities have been attributed to derivatives of ring systems 1-50 in the patent and published literature. New substituted pyrazolo[4,3- pyrimidines have been synthesized and claimed to be useful for treatment of male erectile dysfunction due to the inhibitory action they exerted on phosphodiesterase enzymes <1998EPP995750, 2000USP6066722>. Diverse biological activities have been attributed to pyrazolo[3,4-, pyrimidines... 

Yohimbine (4.43) is an antagonist. Yohimbine, an indole alkaloid closely related to reserpine—an a antagonist—has been evaluated as a potential treatment for male erectile dysfunction. Naphazoline (4.46) and other a-agonist imidazoline compounds are nasal decongestants, used by inhalation to decrease swelling of the nasal mucosa. Overdependence on and overuse of these drugs can lead to rebound swelling. 

IC351 Male erectile dysfunction NDA filed ICOS/Lily... 

Alpha2 antagonists have relatively little clinical usefulness. They have limited benefit in male erectile dysfunction. There has... 

Yohimbine Blocks k2 elicits increased central sympathetic activity increased norepinephrine release Raises BP and HR Male erectile dysfunction hypotension May cause anxiety excess pressor effect if norepinephrine transporter is blocked... 

Male Erectile Dysfunction West Midlands Region Development and Evaluation Committee (DEC)... 

Phentolamine has been used in the treatment of pheochromocytoma—especially intraoperatively— as well as for male erectile dysfunction by injection intracavernosally and when taken orally (see below). 

Terrett, N. K. Bell, A. S. Brown, D. Ellis, P. 1996. Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg. Med. Chem. Lett., 6,1819-1824. 

A dramatic example occurs in the last stage of the production of sildenafil 63 the Pfizer treatment of male erectile dysfunction better known as Viagra . The cyclisation of 62 must involve the attack of the nitrogen atom of one amide on the carbonyl atom of the other (arrows show first stage). This is an exceptionally difficult reaction amides are very poor nucleophiles and very poor electrophiles. Yet this reaction goes in over 90% yield.14 It does so because it is intramolecular. 

Pfizer s Sildenafil (Viagra ) has attracted world-wide attention as a drug for the treatment of male erectile dysfunction."-12 Our synthesis of this important molecule (Scheme 9) demonstrates the principles of using supported reagents in both a sequential and convergent fashion.13 We believe that these concepts could be easily extended to encompass the synthesis of many other chemical substances in target directed synthesis or in a multi-parallel mode. 

Sildenafil (Viagra , Pfizer), the first drug effective in male erectile dysfunction (MED), has a very interesting history. More than 30 years ago, the company May Baker started research on antiallergic xanthine derivatives [19]. Their first leads 27... 

Since most standard medicinal chemistry issues (potency, selectivity, pK, etc.) have been addressed with various inhibitor classes and since three compounds are already on the market, new PDE5 inhibitors in the future may be especially relevant in indications distinct from male erectile dysfunction, as dual (or multiple)-specificity PDE inhibitors, or as templates for the synthesis of other PDE or kinase inhibitors. 

Select drugs or categories, such as those used to treat migraines or male erectile dysfunction, may be subject to quantity limits based on FDA or manufacturer recommendations. For example, Viagra may be limited to 8 tablets per 30 days. 

The potentially life-threatening hypotension caused by an interaction with sildenafil citrate (Viagra), a treatment for male erectile dysfunction, should be highlighted, especially in patients with coronary heart disease needing regular nitrates (6). 

The combination of organic nitrates and sildenafil citrate (Viagra) can precipitate life-threatening hypotension in patients with angina (112). Sildenafil is a selective inhibitor of cyclic GMP-specific phosphodiesterase type 5, which causes smooth muscle relaxation and vasodilatation, and is an effective treatment for male erectile dysfunction. More than 3.6 million prescriptions have been issued as of August 1998, and so far there have been 69 deaths, 12 of which were attributable to the interaction with nitrates, as reported to the FDA. 

Fink HA, Mac Donald R, Rutks IR, Nelson DB, Wilt TJ. Sildenafil for male erectile dysfunction a systematic review and meta-analysis. Arch Intern Med 2002 162(12) 1349-60. 

In the treatment of male erectile dysfunction, direct injection of erectogenic dmgs such as papaverine into the corpus cavernosum is employed. Alternatively, a urethral pellet can be used. Figure 9.57 shows both modes of delivery. The advent of oral treatments with sildenafil will perhaps make this imperfect mode of administration redundant except for those patients in whom oral therapy fails. 

Sildenafil (Viagra) was approved by the FDA in April 1998 for use as an oral therapeutic agent for male erectile dysfunction. It has been found to be a selective inhibitor of phosphodiesterase 5 (PDE5). A high-... 

Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 1996 78 257-61. 

Hawton K. Integration of treatments for male erectile dysfunction. Lancet 1998 351 7-8. 

---