Lu AF60097 might be an efficacious drug candidate for treating depression
Across the globe, over 250 million people suffer from depression, often times, but not always, leading to psychological interventions and drug treatments. And while selective serotonin reuptake inhibitors and tricyclic antidepressants are common choices by clinicans for easing symptoms, side effects are generally a problem.
In a new study by the University of Copenhagen, a research group uncovered a substance that may prove effective for the treatment of depressive disorders, without the serious side effects of conventional antidepressants. The team publicized their findings in the journal Nature Communications.
Lu AF60097, compared to other drugs capable of increasing the production of the neurotransmitter serotonin in the brain, is a substance that binds as serotonin to a site on the serotonin transporter (SERT).
As tested by researchers, the new substance binds to the allosteric site and not the same site as serotonin, as conventional antidepressants do, allowing for more regulation of the serotonin transporter.
For researchers, their primary aim was to establish an efficient antidepressant substance that induces fewer side effects all while treating depressive symptoms with similar therapeutic efficiency as conventional choices.
“The presence of an allosteric site in SERT has been known for more than three decades,” the study’s co-authors stated. “Structurally diverse compounds such as sertraline, paroxetine, clomipramine, and citalopram have been shown to possess allosteric activity as they can impair dissociation of a pre-bound high affinity radioligand to the transporter.”
“We showed that a small amount of Lu AF60097 (1 µl 250 nM) is able to elicit a marked increase of extracellular 5-HT levels in the microdialysis analysis, suggesting that the compound is also capable of targeting SERT in vivo,” the research group affirmed.
“We propose that a clinical potential of the allosteric inhibitor property of Lu AF60097 lies in its potentiation of IMI binding. This might make it possible to lower the therapeutic dose of IMI by co-administering an allosteric binder such as Lu AF60097, preserving the positive effects of tricyclic antidepressants on major depressions while reducing the detrimental side effects,” the findings also determined.
With their new findings on Lu AF60097, the group hopes the substance could be put into further experimentation in the future for the treatment of depression in humans, and possibly down the road, an effective treatment option similar to antidepressants in the market today.