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MADISON, Wis., Aug. 24 -- Erectile dysfunction drugs may enhance sexual pleasure over and above mere performance.

In addition to making intercourse possible for many men with erectile dysfunction, sildenafil (Viagra) and its analogues seem to stimulate release of oxytocin from the pituitary, at least in rats, Meyer Jackson, P.D., of the University of Wisconsin here, and colleagues, reported online in the Journal of Physiology.

Sildenafil, vardenafil (Levitra) and tadalafil (Cialis) are classified as sexual stimulants, not aphrodisiacs, in that they improve sexual function but are not known to affect arousal. They work indirectly to cause smooth muscle relaxation and enhanced blood flow to the penis by inhibiting phosphodiesterase 5 (PDE5), an enzyme that would otherwise break down the smooth muscle relaxant cyclic guanosine monophosphate.

But PDE5 also plays a key role in regulating release of oxytocin from the pituitary, the investigators noted in an early online release from.

"The same stimulation will produce more [oxytocin] release," said Dr. Jackson. "I think this is a missing link in terms of trying to sort out the issues around whether there are additional effects of phosphodiesterase type-5 inhibitors."

Oxytocin is released by the neurohypophysis, or posterior pituitary, during orgasm, and is also involved in milk ejection (letdown) and stimulus of uterine contractions during labor. It has also been shown in animal and human studies to foster maternal attachments to offspring.

"Oxytocin also serves as a signal in central neuronal pathways associated with the erectile response," the investigators wrote. "If PDE5 inhibitors influence central oxytocin nerve terminals in the same way as peripheral nerve terminals of the posterior pituitary, then the activity of these central oxytocin pathways would be enhanced."

The recent findings of two research groups that PDE5 inhibitors enhance sexual function in women as well as in men suggest that the drugs may have other, non-vascular effects, such as hormonal influences, the Wisconsin investigators noted.

They measured oxytocin release from rat pituitaries during neural stimulation. They found that stimulation of the glands in the presence of sildenafil resulted in a three-fold release of oxytocin compared with no sildenafil. In addition, there was little or no effect of sildenafil on oxytocin release in the absence of stimulation, the authors noted.

"Erectile dysfunction drugs do not induce erections spontaneously, they enhance the response to sexual stimulation," Dr. Jackson said. "The same thing is happening in the posterior pituitary: Viagra will not induce the release of oxytocin on its own, but it will enhance the amount of release you get in response to electrical stimulation."

The findings point to new avenues of research into other possible physiologic effects of PDE5 inhibitors.

"A big question raised by our study is, will sildenafil do the same thing to the nerve terminals that release oxytocin?" Dr. Jackson said.

The study was supported by a National Institutes of Health grant. Author conflicts of interest were not reported.

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