Alpha-7 agonist improves cognition in nonsmokers--but not smokers--with schizophrenia

ABT-126—a selective alpha-7 (α7) nicotinic receptor partial agonist—showed improved cognition in patients with schizophrenia but only in those who were nonsmokers, according to a study published online March 4, 2016 in the American Journal of Psychiatry.

Cognitive impairment is a core symptom of schizophrenia, affecting memory, attention, and executive functioning. But no therapies for schizophrenia can noticeably improve cognition.

However, recent research has shown that α7 neuronal nicotinic receptors play a key role in cognitive function, and are known to affect the hippocampus and cerebral cortex—regions that are critical to the synaptic plasticity underlying learning and memory.

In this study, pharmaceutical researchers from Cairo University, in Cairo, Egypt, and AbbVie Inc. (manufacturer of ABT-126) in North Chicago, IL, sought to determine the effectiveness of the α7 agonist ABT-126 in the treatment of cognitive impairment. They recruited 207 clinically stable patients with schizophrenia from 22 centers in the United States, and randomly assigned them to receive a once-daily dose of 10 mg of ABT-126, 25 mg of ABT-126, or placebo.

At the end of the 12-week study period, subjects taking ABT-126 showed overall dose-dependent improvement in cognition (as measured by scores on the MATRICS Consensus Cognitive Battery) compared with subjects taking placebo; however, this overall improvement didn’t reach statistical significance.

When researchers separated smokers from nonsmokers, the drug did show significant effects—but only in nonsmokers. While smokers demonstrated no effects, nonsmokers showed a significant improvement in cognitive score overall, and those in the higher treatment group (25 mg) showed specific improvements in verbal learning, working memory, and attention.

It’s unclear why ABT-126 improved cognition only in nonsmokers, not in smokers. “The current hypothesis is that chronic nicotine exposure from tobacco smoke renders nicotinic receptors ineffective,” the authors wrote.

ABT-126 was generally safe and well tolerated, and subjects remained relatively stable throughout the study—that is, the drug didn’t worsen the underlying psychotic illness, the researchers concluded.