title: Pharmacological approaches to targeting muscarinic acetylcholine receptors.
abstract: The presence of cholinergic system markers and muscarinic receptor subtypes in several tissues also of nonneuronal type has been largely demonstrated. Acetylcholine, synthesized in the nervous system, can locally contribute to modulate cell proliferation, survival and apoptosis. Considering that the cholinergic system functions are impaired in a number of disorders, the identification of new drugs regulating these functions appears of great clinical relevance. The possible involvement of muscarinic acetylcholine receptors in different pathologies has been proposed in recent years and is becoming an important area of study. However, the lack of selective muscarinic receptor ligands has for long time limited the therapeutic treatment based on muscarinic receptors as targets. To date, some muscarinic ligands such as xanomeline (patent, US5980933) or cevimeline (patents US4855290, US5571918) have been developed for the treatment of several pathologies (Alzheimer's and Sjogren's diseases). The present review will be focused on the potential effects produced by muscarinic receptor activation in different pathologies, including tumors. In fact, the potential use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that several muscarinic antagonists, already used in the treatment of genitourinary diseases (e.g. darifenacin, patent, US5096890, US6106864), have also been demonstrated to arrest the tumor growth in vivo. Moreover, the contribution of muscarinic receptors to analgesia is also reviewed. Finally, some of the most significant achievements in the field of bitopic/dualsteric ligands will be discussed and the molecules patented so far will be presented.
authors.forename: Carlo
authors.initials: C
authors.lastname: Matera
authors.affiliation: Dept. of Biology and Biotechnologies Charles Darwin, Research Center of Neurobiology Daniel Bovet, Sapienza, University of Rome, P.le A. Moro, 5 - 00185 Roma, Italy. adamaria.tata@uniroma1.it.
authors.forename: Ada M
authors.initials: AM
authors.lastname: Tata
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000188:drug therapy; D013830:Thiadiazoles / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018721:Muscarinic Agonists; D011725:Pyridines; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D013830:Thiadiazoles; D013876:Thiophenes; C075257:xanomeline; C059240:cevimeline