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Lecture "Mechanisms of selective modulation of individual subtypes of muscarinic receptors"

The disruption of muscarinic signalling is frequently involved in various pathophysiological conditions, including neuropathic pain, neurological and psychiatric disorders, e.g., Alzheimer's disease or schizophrenia. To target these particular conditions, selective modulation of individual muscarinic subtypes to avoid undesired side effects is necessary. High homology of the orthosteric binding site among all muscarinic subtypes makes a finding of orthosteric agonists that bind selectively to individual muscarinic subtypes virtually unattainable. Differences in receptor-membrane interactions or selective targeting at a particular G-protein mediated signalling pathway by biased agonists, via agonist-specific conformation, represent the possibility how to achieve functional selectivity among individual subtypes of muscarinic receptors.