mGluR2 positive allosteric modulators: an updated patent review (2013-2018).
INTRODUCTION
Positive allosteric modulation of mGlu2 has attracted much interest as an alternative approach to classical orthosteric receptor activation. Two mGlu2 PAMS have advanced into the clinic. The results obtained in schizophrenia and MDD phase 2 clinical trials have tempered the high expectations put on selective mGlu2 receptor activation for treating these conditions; nevertheless, the search for novel therapeutic indications and novel chemotypes continues to be an active field of research.


AREAS COVERED
2013-2018 patent literature on mGlu2 receptor PAMs.


EXPERT OPINION
After a decade of intensive research, the mGlu2 PAM field has seen a deceleration in the last five years. Negative phase 2 schizophrenia clinical trials with JNJ-40411813 and AZD8529 seem to have tempered the high expectations of the scientific community on the utility of mGlu2 PAMs for the treatment of schizophrenia. Nevertheless, novel therapeutic indications continue to be explored and AZD8529 is currently in a phase 2 study for smoking cessation. The advances in medicinal chemistry and in pharmacology, with novel indications such as epilepsy, have set the stage in the field of mGlu2 receptor PAMs. Ongoing preclinical and clinical studies will contribute to define their optimal therapeutic indication and potential to become novel therapeutic agents.
['Trabanco|Andrés A|AA|', 'Bartolomé|José Manuel|JM|', 'Cid|José María|JM|']
D000494:Allosteric Regulation D000818:Animals D003865:Depressive Disorder, Major D006801:Humans D007211:Indoles D010069:Oxadiazoles D010330:Patents as Topic D010880:Piperidines D011728:Pyridones D018094:Receptors, Metabotropic Glutamate D012559:Schizophrenia
positive allosteric modulator mGlu2 PAM Metabotropic glutamate receptor 2