New, additional substance seen to alleviate side effects of strong antidepressants
The antidepressants used today block the return transport of serotonin and thereby also the removal of active serotonin, a chemical that plays a major role in regulating our levels of happiness. Such a blockage would require large doses of the antidepressant, which can consequently bring risks of their own such as weight problems, drowsiness, dry mouth and impacts on blood pressure. However, a new substance can be added to the antidepressant mix to lower the required dosage and alleviate side effects, according to scientists from the University of Copenhagen (UCPH) in Denmark.
Modern antidepressants typically work by binding to the same site as serotonin on the serotonin transporter (SERT). Severe forms of depression may call for stronger antidepressants than those administered to mild and moderate sufferers, including tricyclic antidepressants, which can cause serious side effects.
The scientists spent a long time screening substances in the lab to find a one that binds to an alternate location on the SERT known as the allosteric site. The new binding would enable regulation of the SERT, as opposed to blocking it altogether, thereby boosting the performance of tricyclic antidepressants. A substance called Lu AF60097 was found to do the trick – in experiments in cells and on rats, the substance demonstrated “pronounced, pharmacological effects” on both.
UCPH’s Claus Juul Løland explains, “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.
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 scientists thus hope Lu AF60097 paves the way for safer forms of treatment that can be tolerated by more sufferers of the illness and would someday become a clinically approved drug to treat severe depression.
Category: Features, Pharmaceuticals
