Neuroscientists at Johns Hopkins Medical School have found that compound CGP3466B successfully delivers antidepressant effects to mice within mere hours. This compound, which has previously been shown to block cocaine craving in mice, rapidly delivers antidepressant effects when compared to most drugs, which can take weeks or even months.
Dr. Solomon Snyder, professor of neuroscience at the Johns Hopkins University School of Medicine, is optimistic about the medication’s implications, as he has reported that CGP3466B targets a new network of proteins. According to Snyder, this could mean that the compound will be effective in patients who are unresponsive to other types of medications.
“[The compound] lays the foundation for the development of a new class of fast-acting antidepressants that target the same network,” Solomon said.
The compound’s discovery derives from studies done to investigate prospective uses of ketamine, a drug used at high doses to induce anesthesia. Hoping to find a place for CGP3466B in pharmaceuticals, Snyder is optimistic about what the compound means for the future of antidepressants, despite knowing that ketamine is addictive and unsuitable for prolonged use because it produces schizophrenia-like symptoms.
Ketamine interacts with excitatory NMDA receptors on nerve cells in the brain to block their activity. Maged Harraz, a researcher at the School of Medicine, has used biochemical tests on mouse cells to shed light upon the steps responsible for ketamine’s NMDA-blocking antidepressant abilities. The drug, in fact, stimulates the creation of GAPDH and Rheb proteins that help build certain connections between nerve cells.
CGP3466B works in a similar way to ketamine, but it is involved in a role later on in the mechanism of steps and therefore has less side effects. To determine the compound’s effects, experiments were done to see how quickly mice gave up on escaping a pool of water. The group of mice that was given CGP3466B was reported to have spent an extra 30 seconds working through the problem, which the researchers considered a sign of nondepressed behavior. Similarly, mice given CP3466B were twice as fast at entering an unsheltered area to retrieve food when compared to a control group.
The Hopkins team is hopeful that the newly discovered compound can make a difference in the future of antidepressant drug-making, since it has been shown to be nontoxic and non-addictive early on.
However, the researchers warn that it will take a few more years before the compound is in phase II clinical trials. These trials will be necessary in order to determine if the drug has use for humans.
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