Antidepressants in the class known as selective serotonin reuptake inhibitors (SSRIs), which debuted more than 20 years ago, have also been associated with adverse events such as suicidal thinking. The first generation of such drugs, which included Prozac, was notorious, too, for lesser side effects, including stomach upset and sexual dysfunction. Subsequent generations of SSRIs addressed some of those issues by building in blockers of certain serotonin receptor subtypes to eliminate unwanted drug actions.
“As with serotonin, people discovered there are subtypes of [receptor] subtypes. I think as time goes on there will be more sophisticated [nicotinic] drugs coming out,” says Edward D. Levin, a behavioral pharmacologist at Duke University, who has consulted for Targacept and for the National Institutes of Health.
“It’s just like the SSRIs,” Role agrees. “I think refining the compounds in terms of the balance of their activities is really key, but that’s not to say that’s trivial. It’ll take time.” Targeting nicotinic receptors “has enormous therapeutic potential,” she says, adding that the biggest joke on the tobacco industry may be that they missed seeing it.
Note: This story was originally printed with the title, "First in Class".