Muscarinic acetylcholine receptors are membrane receptors involved in many physiological processes. Malfunction of muscarinic signaling is a cause of various internal diseases, as well as psychiatric and neurologic conditions. Cholesterol, neurosteroids, neuroactive steroids, and steroid hormones are molecules of steroid origin that, besides having well-known genomic effects, also modulate membrane proteins including muscarinic acetylcholine receptors. Here, we review current knowledge on the allosteric modulation of muscarinic receptors by these steroids. We give a perspective on the research on the non-genomic effects of steroidal compounds on muscarinic receptors and drug development, with an aim to ultimately exploit such knowledge.

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo Namesti 2 Prague 6 166 10 Prague Czech Republic

Institute of Physiology Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

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Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids