Creating a better drug to treat psychiatric disorders

by Raymond Booth

I first became interested in drugs to treat brain diseases with I was a pharmacy student at Northeastern in the early 1980s. After I got my PhD in medicinal chemistry at the University of California–San Francisco, I returned to Boston for a post-doctoral fellowship at Harvard Medical School.

At the time, I was drawn to research on neurodegenerative diseases, such as Parkinson’s. But by 1987, I switched to neuropsychiatric diseases, and that’s what I’ve been focused on ever since.

Specifically, I’ve been working on developing a drug that’s more effective at treating neuropsychiatric disorders—from schizophrenia to compulsive behavior like drug and alcohol abuse—without the side effects of existing medications. I’ve probably made about 100 compounds to get to the right one—called bromopatin—and it is just about ready for human clinical trials.

But I need to back up a bit to explain the science involved.

Bromopatin is designed to regulate a neurotransmitter called serotonin. Neurotransmitters are chemicals released by nerve cells—neurons—that tell adjacent cells to do or not do something by binding to specific receptors on the target cell. Serotonin plays a key role in neurological processes, including aggression, anxiety, and mood.

When the level of serotonin is out of balance—too much or too little—or the serotonin receptors are damaged by an injury to the brain, a psychiatric or behavioral disorder can result.

For that reason, a variety of antidepressants and antipsychotics target serotonin receptors, but the formulas lack the nuance to fine-tune neurotransmission imbalances.

This is the challenge, and it takes years to overcome because there are certain complexities built into this kind of drug design.

For example, neuroscientists have identified several different kinds of serotonin receptors. To design the right molecule, we need to understand the receptor that we want to target, its characteristic functions, and whether we want to block or activate its effects. And with regard to substance abuse, a new drug needs to be effective in treating not only the addictive behavior, but also the accompanying psychiatric disorders, such as the inability to distinguish fantasy from reality.

Bromopatin constitutes a novel approach, suppressing the activity of some serotonin receptors while elevating activity at other points. And preclinical testing shows no serious side effects—the sedation, neurological disorders, and extreme weight gain that come with current medications and discourage patients from sticking to their treatment plans.

So the next step is clinical trials with human subjects. I am in the process of talking to a number of Boston-area pharmaceutical-development companies about starting that phase.

If all goes well, the drug will be available in a few years to help the millions of families that are now living with chronic conditions like schizophrenia and drug addiction and their debilitating consequences.

Raymond G. Booth is a professor of pharmaceutical sciences and chemistry and a member of Northeastern’s Center for Drug Discovery. His work is funded by the National Institutes of Health.

This story was originally posted on News@Northeastern.

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