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| Johns Hopkins' Maged Harraz |
For years now ketamine has been an alluring target for investigators looking to conquer depression.
In academic study after academic study, the anesthetic and horse tranquilizer has provided a fast and effective treatment for severe depression. The problem is that the NMDA receptor antagonist is also an addictive, ephemeral party drug, Special K, with wide-ranging activity that can trigger hallucinations and schizophrenia-like symptoms, making it impossible to use for anything that requires prolonged dosing.
Now a group of investigators at Johns Hopkins say that they've found a possible substitute that targets the proteins GAPDH and Rheb. The drug, CGP3466B, which was highlighted at Johns Hopkins for its ability to prevent cocaine addiction in another mouse study back in 2013, prevents the addition of nitric oxide to GAPDH, preventing GAPDH from interacting with Rheb and continuing the chain reaction's signaling.
"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 lead author Maged Harraz. As in many other ketamine studies, the researchers also observed a fast onset in the treatment response. And they were encouraged by earlier safety data gathered during earlier, failed studies for Lou Gehrig's disease and Parkinson's.
"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."
J&J ($JNJ) is still working on a new formulation of ketamine that it hopes will prove effective, while AstraZeneca ($AZN) and others have tried and failed at. Allergan recently acquired a late-stage NMDA drug in its acquisition of Naurex last year for $560 million.
- here's the release