2-Methyl-6-(phenylethynyl)pyridine
Encyclopedia
2-Methyl-6-pyridine (MPEP) is a research drug which was one of the first compounds found to act as a selective antagonist for the metabotropic glutamate receptor
subtype mGluR5
. It was developed by the pharmaceutical company Novartis
in the late 1990s. It was found to produce neuroprotective effects following actute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, and as a positive allosteric modulator of another subtype mGlu4
, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant
and anxiolytic
effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.
The main significance of MPEP has been as a lead compound to develop more potent and selective mGluR5 antagonists such as MTEP, but research using MPEP itself continues, and recently it was shown to reduce self-administration of nicotine, cocaine, ketamine and heroin in animals, possibly through an MPEP-induced potentiation of the rewarding effect of the self-administered drug, and MPEP was also shown to possess weak reinforcing effects by itself.
Metabotropic glutamate receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs...
subtype mGluR5
Metabotropic glutamate receptor 5
Metabotropic glutamate receptor 5 is a protein that in humans is encoded by the GRM5 gene.- Function :The amino acid L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors...
. It was developed by the pharmaceutical company Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
in the late 1990s. It was found to produce neuroprotective effects following actute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, and as a positive allosteric modulator of another subtype mGlu4
Metabotropic glutamate receptor 4
Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.Together with GRM6, GRM7 and GRM8 it belongs to group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.Activation of GRM4 has...
, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
and anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.
The main significance of MPEP has been as a lead compound to develop more potent and selective mGluR5 antagonists such as MTEP, but research using MPEP itself continues, and recently it was shown to reduce self-administration of nicotine, cocaine, ketamine and heroin in animals, possibly through an MPEP-induced potentiation of the rewarding effect of the self-administered drug, and MPEP was also shown to possess weak reinforcing effects by itself.