Forskolin: A promising new adjunct to intracavernous pharmacotherapy

Purpose: To evaluate the utility of forskolin as a potentially novel intracavernous therapy. Materials and Methods: Forskolin- and prostaglandin E₁ (PGE₁)-induced intracorporal pressure changes were evaluated in vivo by cavernosometry performed on 2 male mongrel dogs, while systemic pressure changes were simultaneously monitored. Forskolin- and PGE₁-induced intracellular cAMP accumulation was measured in vitro on homogeneous explant cultures of canine corporal smooth muscle cells. Results: Forskolin and PGE₁ elicited concentration-dependent increases in cAMP accumulation in cultured canine corporal smooth muscle cells. Forskolin and PGE₁ also elicited concentration-dependent increases in both the magnitude and duration of intracorporal pressure, up to a maximum of 80 to 90% of mean arterial pressure. Furthermore, the presence of threshold concentrations of forskolin was shown to significantly augment the activity of PGE₁ both in vitro (increased cAMP) and in vivo (increased pressure). Moreover, there were no detectable systemic effects following the intracorporal injection of forskolin or a mixture of forskolin and PGE₁. Conclusions: These observations suggest that the use of forskolin, alone or in combination with other drugs that increase intracellular cAMP levels, might represent an attractive opportunity for improved and more rational development of next generation intracavernous pharmacotherapeutic agents.