
For a depressed patient, SSRIs (Selective serotonin reuptake inhibitors) can take weeks to be effective. Additionally, they are not effective at all in some patients and come with numerous possible side effects. However, scientists have come up with a compound that could potentially evade these problems. The preliminary results are quite positive.
A study was published on 28th October, with some researchers describing how they made a compound that disrupts a composite between neuronal nitric oxide synthase (nNOS), an enzyme, and a protein called SERT, that transports serotonin into the cells and out. The test in mice saw an antidepressant outcome after a couple of hours of administration. Harmful side effects were not found.
SSRIs are expected to partly work through outcomes on the 5-HT1a receptor. In some areas of the brain, attaching to this receptor enables the availability of serotonin to the cells, like in the hippocampus.
However, in the DRN (dorsal raphe nucleus), 5-HT1a, the primary source of serotonin in the brain, performs another way. The same attachment to the receptor stops the cells from firing. This impacts the serotonin concentrations downstream and signals from the DRN encourage the release of serotonin in the cortex. This is a reason for the delayed response to antidepressants.
The 5-HT1a receptors in DRN start to become less sensitive mere weeks after the commencement of SSRI treatment. The team at Nanjing Medical University was of the opinion that they could lower the time between the delivery and effect of the treatment through the release of serotonin from the DRN neurons. Prior studies show that upon the interaction of nNOS and SERT, the receptors stop the cells from firing. The researchers theorized that a SNIB (SERT-nNOS interaction blocker) would speed up the process of symptom relief.
As it was suggested by other researchers, the scientists began by evaluating if the link between nNOS and SERT played a part in the depression. They studied mice previously exposed to chronic mild stress, and it was revealed that there was a link between higher nNOS-SERT complex concentrations in the DRN and more depressive behavior. With all else constant, knocking out the nNOS gene had reverse results as the mice showed greater antidepressant behavior in comparison to others.
Scientists inserted a chemical to separate nNOS and SERT directly into the DRN to check how the breakdown would affect serotonin arrangement. They witnessed a higher SERT activity and an increased antidepressant action within a couple of hours. They also saw increased serotonin levels in the prefrontal cortex, which means that amending the complex caused the fast-paced antidepressant effect.
With these positive results, the scientists made a molecule to break down nNOS and SERT. The molecule was intravenously administered to a number of depressed mice. Results were similar to prior experiments as the depressive behaviors were overturned within a couple of hours. Further tests revealed that the molecule had no effect on cognition, memory, or aggression, and neither did it result in abnormal brain activity. The results are better compared to other drugs that are tested for depression, like ketamine, which causes side effects similar to schizophrenia.