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Biotech / Medical : VVUS: VIVUS INC. (NASDAQ) -- Ignore unavailable to you. Want to Upgrade?

To: Bull-like who wrote (2601)	11/19/1997 11:47:00 PM
From: Bradpalm1	Respond to of 23519

Bull-like, If you're involved in PDE research, please clear up some confusion I have about these isoenzymes. For PGE-1 (alprostadil) and forskolin (as mentioned in one of TA's previous posts) to be successful in initiating cavernosal relaxation, the amount of PDE IV (cAMP-specific) in penile smooth muscle must be significant. Wouldn't this argue for the necessity of these agents (including VIP I suppose) to be only delivered locally due to the ubiquity of this enzyme and the possibility of severe systemic effects? Do you also know if ICOS' experimental ED product is a PDE V (cGMP-specific) inhibitor analogous to sildenafil? Thanks, Bradpalm1

To: Bull-like who wrote (2601)	11/20/1997 8:47:00 AM
From: Bradpalm1	Read Replies (1) \| Respond to of 23519

Bull-like, I think I partially answered my own question. PGE-1&2, forskolin and VIP are DIRECT activators of adenylate cyclase which in turn increases cAMP and doesn't require mediation through PDE isoenzymes. Nitric oxide, on the other hand, directly activates guanylate cyclase and increases cGMP via an analogous mechanism. Inhibition of PDE III, IV & V isoenzymes would still seem to result in penile smooth muscle relaxation although it appears that PDE V is more specific to this area. Doesn't papaverine act as a nonspecific PDE inhibitor? Great news about FDA recertification (cGMP, not the other cGMP). UK approval is next. Bradpalm1