Metabotropic glutamate receptor 4 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''GRM4''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Together with GRM6, GRM7 and GRM8 it belongs to group III of the

metabotropic glutamate receptor The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic receptor, metabotropic process. They are members of the group C GPCR family, group C family of G-protein-coupled r ...

family. Group III receptors are linked to the inhibition of the cyclic AMP cascade. Activation of GRM4 has potential therapeutic benefits in the treatment of

parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

Splice variant Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included ...

"taste-GRM4" is involved in the perception of

umami Umami ( from ), or savoriness, is one of the five basic tastes. It is characteristic of broths and cooked meats. People taste umami through taste receptors that typically respond to glutamates and nucleotides, which are widely present in me ...

taste.

Ligands

Orthosteric

* Cinnabarinic acid, a tryptophan metabolite *LSP1-2111: agonist * LSP4-2022: agonist *

LSP2-9166 LSP2-9166 is a drug which acts as a selective agonist for the group III metabotropic glutamate receptors, with a reasonably potent EC50 of 70nM at mGluR4 and 220nM at mGluR7, and weaker activity of 1380nM at mGluR6 and 4800nM at mGluR8. It ha ...

: mixed agonist at mGluR₄ and mGluR₇

Positive allosteric modulators (PAMs)

ADX88178 ADX88178 is an experimental drug that acts as a positive allosteric modulator for the glutamate receptor mGluR4. It was developed as a potential medication for the treatment of Parkinson's disease Parkinson's disease (PD), or simply Parkins ...

Foliglurax Foliglurax (developmental code names PXT-002331, DT2331) is a positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4), which is under development by Prexton Therapeutics for the treatment of Parkinson's disease. It reache ...

(PXT-002331, DT-1687) * Tricyclic thiazolopyrazole derivative 22a: EC₅₀ = 9 nM, E_max = 120% *

ML-128 ML-1 was an experimental nuclear reactor built as part of the US Army Nuclear Power Program between 1961 and 1965. It was intended to provide truck-mounted nuclear power that could accompany troops from place to place and provide power to comm ...

: EC₅₀ = 240 nM, E_max = 182% *

Valiglurax Valiglurax (VU0652957) is an experimental drug that is a positive allosteric modulator for the glutamate receptor mGluR4. It was developed as a potential medication for the treatment of Parkinson's disease Parkinson's disease (PD), or simp ...

(AP-472) (VU0652957) * VU-0418506 * VU-001171: EC₅₀ = 650 nM, E_max = 141%, 36-fold shift *

VU0155041 VU0155041 is an experimental drug that is a positive allosteric modulator for the glutamate receptor mGluR4. In animal studies it has anti-Parkinsonian action, reduces neuropathic pain such as allodynia, and counteracts the effects of opioid ...

: subtype-selective PAM, intrinsic allosteric agonist activity, robust in-vivo activity * VU0364770 *

PHCCC PHCCC is a research drug which acts as a glutamate receptor ligand, particularly being a positive allosteric modulator at the mGluR4 subtype, as well as an agonist at mGluR6. It has anxiolytic effects in animal studies. PHCCC and similar drugs ...

: PAM of mGluR4, negative allosteric modulator of

mGluR1 The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 (mGluR1) protein. Function L-Glutamate is the major excitatory neurotransmitter in the central nervous system and ...

, direct agonist at

mGluR6 Glutamate receptor, metabotropic 6, also known as GRM6 or mGluR6, is a protein which in humans is encoded by the ''GRM6'' gene. Function L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ion ...

* TC-N 22A

Ligands

Orthosteric

Positive allosteric modulators (PAMs)

References

Further reading