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HMP-12 an adrenoceptor antagonist for the treatmen

Posted on: 25 Oct 02

Summary

LeadDiscovery is pleased to announce the completion of it's most recent DiscoveryDossier describing a new licensing or co-development opportunity relating the treatment of erectile dysfunction and fem
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Sildenafil became a blockbuster treatment of erectile dysfunction almost overnight, with sales reportedly totaling $1.5 billion in 2001. Despite the success of sildenafil and improvements that are expected with the development of second-generation PDE5 inhibitors, this approach remains unsuitable for 30-50% of patients due to the severity of disease or to contra-indications. A sizable market therefore remains for the treatment of erectile dysfunction; however, of greater commercial significance is perhaps the female sexual dysfunction market. According to the much-quoted JAMA article published in 1999, more American women (43%; about 40 million) than men (31%) experience some form of sexual disorder. Female sexual dysfunction represents a family of conditions that have few pharmacological therapies. Of interest, and in contrast to males, the distribution of female dysfunctions is fairly even among women ranging from 18 to 59 years of age. Approximately 20% of women with female sexual dysfunction suffer arousal disorder characterized by either a failure of vaginal engorgement/lubrication or an altered appraisal of arousal, and it has been suggested that treatments of female arousal disorder represent a market of similar size to that of erectile dysfunction. Female arousal disorder and moderate to severe erectile dysfunction thus represent indications with blockbuster potential. Due to the similarities between the corpus cavernosum and the clitoris with respect to both structure and innervation, a number of pharmacological targets may be appropriate for both indications. In August, 2002, LeadDiscovery published a state of the art review of sexual dysfunction targets and the pharmaceutical activity surrounding these targets (click here to access). Here we focus on the involvement of adrenoceptors in male and female sexual physiology, and in the pathophysiology of erectile dysfunction and female arousal disorder. The adrenoceptor antagonist, phentolamine has been launched for the treatment of erectile dysfunction and is in clinical development for the treatment of female arousal disorder. This report analyses the development of MDI's novel adrenoceptor antagonist, HMP-12 which is a more potent antagonist of corpus cavernosal contraction than phentolamine and is also able to stimulate vaginal blood flow. We conclude that although adrenoceptor antagonists are unlikely to replace PDE5 inhibitors as treatments of mild erectile dysfunction, such molecules may provide a valuable adjunct to PDE5 inhibitors (or indeed apomorphine) in treating the 50% of patients with moderate to severe disease that are poorly responsive to sildenafil monotherapy. Perhaps more important, adrenoceptor antagonists stand to become the first non-HRT treatment of female arousal disorder in post-menopausal women, and maybe in addition a valuable approach to pre-menopausal women with sexual dysfunctions. Drug development analysis shows that although a large number of adrenoceptor antagonists have been developed few of these are indicated for erectile dysfunction or female arousal disorder, due in part to the selectivity of most of this products to a1 or a2 receptors suggesting that novel mixed adrenoceptor antagonists may be relatively free of competition. HMP-12 therefore offers excellent therapeutic and commercial prospects and MDI are now seeking partners to optimize the development of this potential. For free access to this dossier Click here or paste the following address into your browser:

http://www.leaddiscovery.co.uk/dossiers/MDI002/MDI.html

Dr Jon Goldhill

Last updated on: 27/08/2010 11:40:18

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