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When it comes to antidepressants, two may be better than one. When drugs that alter two mood-regulating brain chemicals — serotonin and acetylcholine — are combined, they work together to produce a greater antidepressant response, a new animal study shows.

The research was presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience, held in San Diego.

“Although we have many therapies available to help alleviate the symptoms of depression, current treatments, which include the popular selective serotonin reuptake inhibitor [SSRI] medications, are effective in only about 50 percent of patients,” said Marina Picciotto, PhD, of Yale University, the study’s senior author. “Our study suggests that combination therapies could be beneficial in patients non-responsive to SSRIs,” she said. SSRIs, which increase serotonin levels in the brain, have long been used to treat depression. More recently, animal studies and a few clinical trials have suggested that another brain chemical, acetycholine, plays an important role in regulating mood. Medicines that block some of the nerve receptors for acetylcholine can be antidepressant.

Picciotto and her colleagues found that combining the SSRI fluoxetine (Prozac) with cytisine, a drug that limits the effects of acetylcholine, produced greater antidepressant-like properties in mice than when the drugs were used alone. They also discovered that when serotonin was removed from the animals’ brains, cytisine was no longer effective.

“This suggests that serotonin is critical for cytisine’s antidepressant-like effects,” Picciotto said.

Research was supported by the National Institute of Mental Health and NARSAD. Dr. Picciotto has a proprietary interest in developing several nicotinic partial agonists for the treatment of depression, none of which were used in the current study.

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