Muscarinic acetylcholine receptors as therapeutic targets for obesity
- 12 August 2008
- journal article
- review article
- Published by Informa Healthcare in Emerging Therapeutic Targets
- Vol. 12 (9), 1167-1175
- https://doi.org/10.1517/14728222.12.9.1167
Abstract
Background: There are five types of muscarinic acetylcholine receptors (mAChRs), M1 – M5, which regulate several central and peripheral functions. Transgenic mice deficient in these receptors have been generated. Objective: To understand some processes in which these receptors are involved, mainly targeting obesity, which seems to be mediated by M3 in the hypothalamus. Methods: The absence of M3 has beneficial effects, which protect mice against some forms of obesity and ameliorate glucose and energy homeostasis. These findings suggest some relevance of muscarinic M3 antagonists to the treatment of obesity, and also studies with new classes of M3-receptor selective antagonists, to identify active/selective molecules, able to reach the CNS, which might have fewer side-effects compared with available muscarinic drugs. Results/conclusion: M3 antagonists might have application to the design of antiobesity agents. However, this research is in its preliminary phases, and the lack of specific antagonists or agonists for M3 receptors in CNS, make it impossible to validate this antiobesity target at present.Keywords
This publication has 22 references indexed in Scilit:
- Muscarinic acetylcholine receptors: mutant mice provide new insights for drug developmentNature Reviews Drug Discovery, 2007
- Discovery of Diaryl Imidazolidin-2-one Derivatives, a Novel Class of Muscarinic M3 Selective Antagonists (Part 1)Journal of Medicinal Chemistry, 2007
- Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiencyCell Metabolism, 2006
- Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladderBritish Journal of Pharmacology, 2006
- Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampusProgress in brain research, 2004
- Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and leanNature, 2001
- New insights into sympathetic regulation of glucose and fat metabolismDiabetologia, 2000
- From Lesions to LeptinNeuron, 1999
- Hypocretin/Orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: Relationship to the neuropeptide Y and agouti gene-related protein systemsJournal of Comparative Neurology, 1998
- Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic areaJournal of Comparative Neurology, 1998