Related Research Articles
Benzatropine (INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is not useful for tardive dyskinesia. It is taken by mouth or by injection into a vein or muscle. Benefits are seen within two hours and last for up to ten hours.
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers. They are mainly found in the parasympathetic nervous system, but also have a role in the sympathetic nervous system in the control of sweat glands.
Amisulpride, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.
Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease, certain drug-induced movement disorders and Tourette Syndrome. It is not recommended for tardive dyskinesias. It is taken by mouth, injection into a vein, or muscle.
A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.
The human muscarinic acetylcholine receptor M5, encoded by the CHRM5 gene, is a member of the G protein-coupled receptor superfamily of integral membrane proteins. It is coupled to Gq protein. Binding of the endogenous ligand acetylcholine to the M5 receptor triggers a number of cellular responses such as adenylate cyclase inhibition, phosphoinositide degradation, and potassium channel modulation. Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor have not been fully explored; however, stimulation of this receptor is known to effectively decrease cyclic AMP levels and downregulate the activity of protein kinase A (PKA).
The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.
Xanomeline is a small molecule muscarinic acetylcholine receptor agonist that was first synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the treatment of central nervous system (CNS) disorders.
Sabcomeline (Memric; SB-202,026) is a selective M1 receptor partial agonist that was under development for the treatment of Alzheimer's disease. It made it to phase III clinical trials before being discontinued due to poor results.
N-Desmethylclozapine (NDMC), or norclozapine, is a major active metabolite of the atypical antipsychotic drug clozapine.
Tazomeline (LY-287,041) is a drug which acts as a non-selective muscarinic acetylcholine receptor agonist. It was in clinical trials for the treatment of cognitive dysfunction such as that seen in Alzheimer's disease and schizophrenia, but development was apparently scrapped for unknown reasons. Another of the patented uses is for the treatment of "severe painful conditions".
VU-0238429 is a drug which acts as a selective positive allosteric modulator for the muscarinic acetylcholine receptor M5. It was the first selective ligand developed for the M5 subtype, and is structurally derived from older M1-selective positive allosteric modulators such as VU-0119498. Replacing the O-methyl- by a phenyl group further improves the receptor subtype selectivity.
AFDX-384 (BIBN-161) is a drug which acts as a selective antagonist of the muscarinic acetylcholine receptors, with selectivity for the M2 and M4 subtypes. It is used mainly for mapping the distribution of M2 and M4 muscarinic receptors in the brain, and studying their involvement in the development and treatment of dementia and schizophrenia.
Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).
Xanomeline/trospium chloride, sold under the brand name Cobenfy, is a fixed-dose combination medication used for the treatment of schizophrenia. It contains xanomeline, a muscarinic agonist; and trospium chloride, a muscarinic antagonist. Xanomeline is a functionally preferring muscarinic M4 and M1 receptor agonist. Trospium chloride is a non-selective muscarinic antagonist.
Emraclidine is an investigational antipsychotic for the treatment of both schizophrenia and Alzheimer's disease psychosis developed by Cerevel Therapeutics. As of August 2024, it is in phase 2 clinical trials.
NBI-1076968 is a selective muscarinic acetylcholine M4 receptor antagonist which is under development by Neurocrine Biosciences for the treatment of movement disorders. It is orally active.
NS-136 is a selective muscarinic acetylcholine M4 receptor positive allosteric modulator which is under development for the treatment of schizophrenia and Alzheimer's disease. It has been found to possess pro-cognitive effects in rodents. The drug is under development by NeuShen Therapeutics. As of May 2024, it is in phase 1 clinical trials for schizophrenia and is in the preclinical stage of development for Alzheimer's disease. The drug is a small molecule, but its chemical structure does not seem to have been disclosed.
Itameline is a non-selective muscarinic acetylcholine receptor agonist which was under development for the treatment of Alzheimer's disease and memory disorders but was never marketed. It has been referred to as a "nootropic".
References
- 1 2 3 4 5 6 7 "ML 007". AdisInsight. Springer Nature Switzerland AG. 9 January 2024. Retrieved 21 October 2024.
- 1 2 3 4 "Delving into the Latest Updates on ML-007 with Synapse". Synapse. 19 September 2024. Retrieved 21 October 2024.
- 1 2 3 Yohn SE, Harvey PD, Brannan SK, Horan WP (4 October 2024). "The potential of muscarinic M1 and M4 receptor activators for the treatment of cognitive impairment associated with schizophrenia". Frontiers in Psychiatry. 15. Frontiers Media SA. doi: 10.3389/fpsyt.2024.1421554 . ISSN 1664-0640. PMC 11525114 .
- 1 2 3 Walker LC, Huckstep KL, Becker HC, Langmead CJ, Lawrence AJ (November 2024). "Targeting muscarinic receptors for the treatment of alcohol use disorders: Opportunities and hurdles for clinical development". British Journal of Pharmacology. 181 (22): 4385–4398. doi: 10.1111/bph.16081 . PMID 37005377.
 | This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it. |