New substance alleviates the side effects of strong antidepressants
Modern antidepressants can be a vital tool in helping patients cope with their condition, but they can also bring risks of their own, including side effects such as weight problems, drowsiness, dry mouth and impacts on blood pressure. Scientists at the University of Copenhagen have discovered a new substance that could be added to the mix to lower the required dose of antidepressants and alleviate these side effects, paving the way for safer forms of treatment that can be tolerated by more sufferers of the illness.
Severe forms of depression may call for stronger antidepressants than those administered to mild and moderate sufferers. One example of these are tricyclic antidepressants, which alter the brain chemistry by interfering with the movement of serotonin, a chemical that plays a major role in regulating our levels of happiness.
"The antidepressants we use today work by going in and binding to the same site as serotonin on the serotonin transporter (SERT)," says study author Claus Juul Løland. "The antidepressants block the return transport of serotonin and thereby also the removal of the active serotonin. But such blockage requires a relatively large dose of the antidepressant substance. And with the tricyclic antidepressants, that causes some serious side effects."
Løland and his colleagues have spent a long time screening substances in the lab that could alter this process. The hope was that they could find a substance that binds to an alternate location on the SERT known as the allosteric site, which would enable regulation of the SERT as opposed to blocking it altogether, thereby boosting the performance of tricyclic antidepressants. And they believe they have finally done so in a substance called Lu AF60097.
"In this case, we have shown that when we bind this substance to the allosteric site while giving the tricyclic antidepressant, we can amplify the binding of the antidepressant substance," says Løland. "Therefore, we can use a much smaller concentration of the antidepressant substance. It might cause fewer side effects, but have the same therapeutic effect."
The team established this through experiments in cells and on rats, demonstrating "pronounced, pharmacological effects" on both. While noting that there is a long way to go before Lu AF60097 becomes a clinically approved drug to treat depression, the team is enthused by the early results.
‘We have taken the first step," says Løland. "But perhaps also the biggest. We have shown that the concept works. If it also works in practice, hopefully in the future it can be used to treat people with severe depression."
The research was published in the journal Nature Communications.
Source: University of Copenhagen