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.


CONCLUSIONS
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.
Maresca
Alfonso
A
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
Supuran
Claudiu T
CT
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*
D019440:Anti-Obesity Agents; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic