FORSKOLIN - A PROMISING NEW ADJUNCT TO INTRACAVERNOUS PHARMACOTHERAPY

Purpose: To evaluate the utility of forskolin as a potentially novel i ntracavernous therapy. Materials and Methods: Forskolin- and prostagla ndin E(1) (PGE(1))-induced intracorporal pressure changes were evaluat ed in vivo by cavernosometry performed on 2 male mongrel dogs, while s ystemic pressure changes were simultaneously monitored. Forskolin- and PGE(1)-induced intracellular cAMP accumulation was measured in vitro on homogeneous explant cultures of canine corporal smooth muscle cells . Results: Forskolin and PGE(1) elicited concentration-dependent incre ases in cAMP accumulation in cultured canine corporal smooth muscle ce lls. Forskolin and PGE(1) also elicited concentration-dependent increa ses in both the magnitude and duration of intracorporal pressure, up t o a maximum of 80 to 90% of mean arterial pressure. Furthermore, the p resence of threshold concentrations of forskolin was shown to signific antly augment the activity of PGE(1) both in vitro (increased cAMP) an d in vivo (increased pressure). Moreover, there were no detectable sys temic effects following the intracorporal injection of forskolin or a mixture of forskolin and PGE(1). Conclusions: These observations sugge st that the use of forskolin, alone or in combination with other drugs that increase intracellular cAMP levels, might represent an attractiv e opportunity for improved and more rational development of next gener ation intracavernous pharmacotherapeutic agents.