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.