Jp. Mulhall et al., INTRACAVERNOSAL FORSKOLIN - ROLE IN MANAGEMENT OF VASCULOGENIC IMPOTENCE RESISTANT TO STANDARD 3-AGENT PHARMACOTHERAPY, The Journal of urology, 158(5), 1997, pp. 1752-1758
Purpose: We investigated forskolin, a direct adenylate cyclase activat
or, as an intracavernosal vasoactive agent in management of vasculogen
ic impotence. Materials and Methods: Concentration responses for forsk
olin and prostaglandin El induced relaxation of phenylephrine precontr
acted strips of human corpus cavernosum smooth muscle were constructed
in vitro. Cyclic adenosine monophosphate (cAMP) synthesis was determi
ned with papaverine, phentolamine, prostaglandin El and forskolin in h
uman corpus cavernosum smooth muscle cell cultures. Dose-dependent hem
odynamic responses to intracavernosal forskolin (5 to 20 mu g.)were ev
aluated in a New Zealand White rabbit model. Safety and efficacy outco
me data were obtained in vasculogenically impotent patients who signed
informed consent and met strict inclusion and exclusion criteria that
included having had standard self-injection therapies fail. Results:
In vitro forskolin and prostaglandin El alone caused concentration dep
endent relaxation with an EC50 of approximately 200 nm, and 16 nm,, re
spectively, When the 2 agents were combined, the concentration respons
e curve for relaxation shifted to the left. cAMP production was highes
t in cells treated with prostaglandin El and forskolin and was unaffec
ted by papaverine or phentolamine. In 3 animals, equilibrium intracave
rnosal pressure and duration of erection had a dose dependent increase
. Clinical investigation in 31 patients showed no adverse events with
a mean of 14 +/- 4, range 11 to 18 months of followup. Overall 61% rep
orted improvement in rigidity and/or erection duration using intracave
rnosal forskolin (98 mu g./ml.), papaverine (29 mg,/ml,), phentolamine
(0.98 mg./ml,) and prostaglandin EB (9.8 mu g./ml.). Conclusions: For
skolin is a United States Food and Drug Administration nonapproved vas
oactive agent that acts in synergism with prostaglandin El to induce s
mooth muscle relaxation. In combination with other vasoactive agents,
forskolin has demonstrated preliminary safety and efficacy in patients
with vasculogenic impotence resistant to standard 3-agent pharmacothe
rapy.