Trial Drug Targets Impotence Via the Brain

Could be useful for those not helped by Viagra

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By
HealthDay Reporter

MONDAY, April 12, 2004 (HealthDayNews) -- A drug that acts in a very different way than Viagra could work for men whose erectile dysfunction is not helped by that popular medication, researchers have found.

Viagra and its two newly marketed rivals, Levitra and Cialis, help men achieve erections by acting on the muscles of the penis, explained Dr. Jorge Brioni, a project leader in neuroscience research at Abbott Laboratories.

The new medication, developed at Abbott and designated ABT-724, "targets the central mechanisms in the brain that control erectile dysfunction in humans," Brioni said.

The drug has been successful in animal tests and has moved into human trials. The full set of trials needed for marketing approval could take seven or eight years, said James P. Sullivan, regional vice president for neuroscience discovery research at Abbott.

There is a need for a different approach because the Viagra-type drugs are not effective in a substantial percentage of men who try them, Sullivan said. "In particular, the response rate is not as great as we would like in patient with diabetes," he said.

ABT-724 is a variation of a drug called apomorphine, which acts on brain receptors of a molecule called dopamine. Abbott markets apomorphine in Europe (but not in the United States) as a treatment for erectile dysfunction. Its success has been limited because it can cause nausea and vomiting.

The key to development of a compound that has the desired effect of apomorphine is the discovery that there are different kinds of receptors for dopamine, Brioni said.

"What we discovered was that the efficacy is mediated by one kind of receptor, while the side effects are mediated by another kind," Brioni said. "That was a significant scientific breakthrough."

A report on the research appears in this week's issue of the Proceedings of the National Academy of Sciences.

Given alone, ABT-724 has successfully induced erections in animal trials and its first human studies. Animal studies show it also increases the effectiveness of Viagra, Sullivan added, "but we believe that the drug can and would be used for the most part as a single agent. The response when it is given alone is as robust as one sees when it is given in combination with Viagra."

One possibility the Abbott researchers are exploring is that a drug that acts on dopamine receptors might be effective in women, in whom Viagra has not worked well, Sullivan said.

"There is a tremendous unmet need in terms of female sexual dysfunction," he said. "Medications that act on muscles are not effective. We need to go to more central underpinnings of sexual function. Here we have a drug with a completely different mechanism. We'd like to speculate that it has potential utility in female sexual dysfunction."

More information

For more on erectile dysfunction, its causes and treatment, visit the National Institute of Diabetes and Digestive and Kidney Diseases or the American Foundation for Urologic Disease.

SOURCES: Jorge Brioni, M.D., project leader, neuroscience research, Abbott Laboratories, Abbott Park, Ill.; James P. Sullivan, regional vice president, neuroscience discovery research, Abbott Laboratories, Abbott Park, Ill.; April 12-16, 2004, Proceedings of the National Academy of Sciences

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