Brain and Body

Ketamine Led Scientists to New, Fast-Acting Antidepressant

January 25, 2016 | Kelly Tatera

A neatly aligned grid pattern of brown and red pills
Photo credit: epSos .de/flickr (CC by SA 2.0)

No more waiting for weeks or months.

Globally, an estimated 350 million people suffer from depression, according to the World Health Organization. Frustratingly, treating depression with antidepressants involves a lot of guesswork and trial and error — plus, many people don’t even respond to the drugs.

Now, researchers at the Johns Hopkins School of Medicine have experimented with a drug called CGP3466B (known to be safe for humans), and this potential new antidepressant could work in just hours, rather than weeks or months.

“One of the promising things about CGP3466B is that it targets a new network of proteins,” says Solomon Snyder, professor of neuroscience at Johns Hopkins University School of Medicine. “That means it may work in patients who are unresponsive to other types of drugs and it lays the foundation for the development of a new class of fast-acting antidepressants that target the same network.”

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How did researchers decide to test out CGP3466B for depression? Interestingly, their inspiration came from the illegal drug ketamine.

At high doses, ketamine is used to induce anesthesia during surgery, but it’s also known to be a fast-acting antidepressant at lower doses. The drug interacts with excitatory NMDA receptors on nerve cells in the brain to block their activity.

However, ketamine is addictive and can produce schizophrenia-like symptoms, so it’s not exactly the best contender for an antidepressant. Luckily, it helped scientists discover the fast-acting antidepressant properties in CGP3466B.

“CGP3466B works on the same network of proteins as ketamine, but since it works later in the chain reaction, it has fewer side effects,” says Maged Harraz, a research associate in neuroscience and first author of the paper published in the journal Molecular Psychiatry.

The scientists used two standard behavioral tests on mice to see whether CGP3466B had ketamine-like antidepressant effects in mammals. In the first test, the scientists observed how quickly the mice gave up trying to escape from a pool of water. Compared to the mice who were given no treatment, the mice who were given CGP3466B spent, on average, an extra half-minute working on the problem.

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In the second test, scientists observed that the mice who were given CGP3466B were twice as fast to brave an unsheltered new environment in order to get a piece of food. Researchers say that the behaviors exhibited in both tests are considered “surrogates for non-depressed behavior.”

“In the second test, the drug worked in only half an hour,” Harraz says. “Other antidepressants tested in mice, like fluoxetine, can take three weeks to show similar results on the same test.”

You likely know Fluoxetine by its common brand name, Prozac, which is one of the most commonly prescribed antidepressants.

The team is optimistic about further experimentation with CGP3466B, but the researchers warn that it will take several more years until the compound reaches phase II clinical trials to test its potential as a safe, fast-acting antidepressant for humans.

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