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Selective positive allosteric modulator of M4 receptor (KB = 200 nM, α = 35); increases the potency of acetylcholine by 40-fold. Exhibits no effect at hM1/3/5 receptors and a small effect at hM2 (KB = 1 μM α = 3.7). Potentiates other full and partial orthosteric agonists, including Carbachol, Oxotremorine-M, and McN-A343. Does not affect binding of antagonist NMS. Active in vivo. Antipsychotic.
α indicates the degree of allosteric enhancement when both orthosteric and allosteric sites are occupied (derived from the allosteric ternary complex model).
|Storage||Store at +4°C|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
The following data is based on the product molecular weight 311.79. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||3.21 mL||16.04 mL||32.07 mL|
|5 mM||0.64 mL||3.21 mL||6.41 mL|
|10 mM||0.32 mL||1.6 mL||3.21 mL|
|50 mM||0.06 mL||0.32 mL||0.64 mL|
References are publications that support the biological activity of the product.
Leach et al (2010) Molecular mechanisms of action and in vivo validation of an M4 muscarinic acetylcholine receptor allosteric modulator with potential antipsychotic properties. Neuropsychopharmacology 35 855 PMID: 19940843
Huynh et al (2015) Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004. ACS Chem. Neurosci. 6 838 PMID: 25857219
Chan et al (2008) Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia Proc.Natl.Acad.Sci.U.S.A. 105 10978 PMID: 18678919
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Keywords: LY 2033298, LY 2033298 supplier, LY2033298, Selective, positive, allosteric, modulators, M4, receptors, PAMs, active, in, vivo, antipsychotic, acetylcholine, modulates, Receptors, 7027, Tocris Bioscience
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Literature in this Area
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Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.
Learning & Memory Poster
Recognition memory enables us to make judgements about whether or not we have encountered a particular stimulus before. This poster outlines the cellular mechanisms underlying recognition memory and its links to long-term depression, as well as the use of pharmacological intervention to assess the role of neurotransmitters in recognition memory.
Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.