Activation of the mGlu1 metabotropic glutamate receptor has antipsychotic-like effects and is required for efficacy of M4 muscarinic receptor allosteric modulators

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https://www.ncbi.nlm.nih.gov/m/pubmed/30116027

“Herein, we report that potentiation of mGlu1 signaling following thalamo-striatal stimulation is sufficient to inhibit striatal dopamine release, and that a novel mGlu1 positive allosteric modulator (PAM) exerts robust antipsychotic-like effects through an endocannabinoid-dependent mechanism. However, unlike M4, mGlu1 does not directly inhibit dopamine D1 receptor signaling and does not reduce motivational responding. Taken together, these findings highlight a novel mechanism of cross talk between mGlu1 and M4 and demonstrate that highly selective mGlu1 PAMs may provide a novel strategy for the treatment of positive symptoms associated with schizophrenia.”

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lets go scientists we need some novel shi

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Nice one, But i thought in the past some PAM drugs where in trial and failed?

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This is from Wikipedia, because I’m not that smart that I understand this, but a PAM (positive allosteric modulator) "is a substance which indirectly influences (modulates) the effects of a primary ligand that directly activates or deactivates the function of a target protein. " so if there was a failed trial at some point, it could have been a PAM of something else.

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Yes that makes sense.

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