If dopamine fails, try glutamate

Happy Labor Day (US)! Topping the NYT most popular articles list right now is an interesting article about a new schizophrenia treatment that targets certain glutamate receptors unlike previous dopaminergic drugs. The drug, which is being developed by Eli Lilly, is partially due to this interesting observation:

For decades, psychiatrists have known that users of PCP, a street drug sometimes called angel dust, have symptoms nearly identical to those of people with schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain receptors that are triggered by an amino acid called glutamate. This led some companies and scientists to study ways to stimulate glutamate receptors as a treatment for schizophrenia.

But the brain has many different kinds of glutamate receptors, and figuring out how to stimulate or block them in medically beneficial ways has proved complicated. Instead of focusing on the receptors blocked by PCP, Dr. Schoepp concentrated on modulating the action of glutamate receptors in the brain’s prefrontal cortex, an area responsible for personality and learning.

The drug, “LY2140023”, is an mGlu2/3 agonist. It showed statistically significant results in a (mid-sized?) clinical trial. Here’s the paper:

Sandeep T Patil, Lu Zhang, Ferenc Martenyi, Stephen L Lowe, Kimberley A Jackson, Boris V Andreev, Alla S Avedisova, Leonid M Bardenstein, Issak Y Gurovich, Margarita A Morozova, Sergey N Mosolov, Nikolai G Neznanov, Alexander M Reznik, Anatoly B Smulevich, Vladimir A Tochilov, Bryan G Johnson, James A Monn & Darryle D Schoepp. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nature Medicine 13, 1102 – 1107 (2007).

Neurocritic also has a blog post about this.

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