Short Introduction to M1 and M4
Five subtypes (M1-M5) of the muscarinic acetylcholine receptors (mAChRs) family can be found throughout the CNS and periphery. The M1 mAChR subtype is expressed in several brain regions which regulate cognitive processes. M4 is a subfamily of G-protein coupled receptors (GPCRs), which plays an important role in spontaneous locomotor activity regulation and modulation of the cholinergic system. Creative Biolabs has rich experience in the development of small molecule drugs. Our top research team provides you with one-stop receptor activators development services which can help you to research psychotropic drugs.
Function of M1 in Psychiatric Disease
M1 knockout (KO) mice that can’t express the M1 receptor were used to exam the function of the M1 receptor. These M1- deficient mice display increased amphetamine-induced hyperlocomotion and dopamine neurotransmission which indicates that M1 modulation may have antipsychotic potential.
M1 mAChRs can increase N-methyl-D-aspartate (NMDA)-receptor signaling in brain areas (hippocampus and cortex) that are intimately associated with learning and memory. Studies in mice exhibiting Alzheimer's disease (AD)-like Aβ plaque pathologies found that the deletion of M1 increased amyloidogenic processes, suggesting that M1 may play a role in regulating AD disease progression.
The Function of M4 in Psychiatric Disease
The M4 receptor is highly expressed in the striatum, hippocampus, and neocortex, which suggests that this mAChR subtype is ideally located to modulate dopaminergic signaling. The same method was used to study the M4 receptor. M4 KO mice, which can't express the M4 receptor, exhibited a hyperdopaminergic phenotype that is resistant to mAChR agonist-induced attenuation of dopamine levels. In addition to KO M4 directly, scientists proved the role of M4 from another side. Selective deletion of M4 mAChRs on D1 dopamine receptor-expressing neurons resulted in increased locomotor activity and behavioral sensitization to psychostimulants. Another preclinical study also showed the role of M4. The antipsychotic efficacy of xanomeline in preclinical animal models is attenuated in animals, in which this subpopulation of M4 receptors is deleted.
What We Can Provide？
The M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia. The bottleneck in receptors studies is producing sufficient quantities of soluble, functional, and stable receptors. To produce sufficient quantities of soluble, functional, and stable receptors, we offer three protocols. Cell-free in vitro translation systems, HEK cells, and Escherichia coli are used to produce and solubilize stable receptors. We can help you to analyze the crystal structures of the different mAChRs. This helps you to better understand their characteristics and lay the foundation for the development of psychotropic drugs. As for further study such as the characterization of receptors in vivo, we can give you some comprehensive support.
GPCRs are integral proteins of the cell membrane and are directly involved in the regulation of many biological functions and drug targeting. Creative Biolabs helps you to develop M1 and/or M4 muscarinic receptor activators. If you have any questions, please contact us.
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