Muscarinic acetylcholine receptors as therapeutic targets for obesity

Background: There are five types of muscarinic acetylcholine receptors (mAChRs), M-1 - M-5, 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 M-3 in the hypothalamus. Methods: The absence of M-3 has beneficial effects, which protect mice against some forms of obesity and ameliorate glucose and energy homeostasis. These findings suggest some relevance of muscarinic M-3 antagonists to the treatment of obesity, and also studies with new classes of M-3-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: M-3 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 M-3 receptors in CNS, make it impossible to validate this antiobesity target at present.