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Lecture "Current advances in pharmacology of muscarinic receptors"

Mgr. Jan Jakubík, PhD, Laboratory of Neurochemistry, IPHYS

Cholinergic signalling via muscarinic receptors plays a vital role in the periphery and central nervous system. In the periphery, muscarinic receptors mediate parasympathetic innervation. In the central nervous system, they are part of cognitive and behavioural processes and memory formation. Altered cholinergic signalling via muscarinic receptors is accompanied by various pathologies. For example, asthma, chronic obstructive pulmonary disease and overactive bladder in the periphery or Alzheimer’s disease, Perkinson’s disease, schizophrenia, epilepsy, mood disorders and addictive behaviour in the central nervous system. Therefore, muscarinic receptors attract pharmacologists for more than a century.

Recently, we have recognised neurosteroids as a novel class of allosteric modulators and identified their binding sites that are distinct from the classical allosteric site located in the extracellular domain. Further, we have conceptualised signalling bias at the level of individual isoforms of G-proteins affording tissue-selective pharmacology. Finally, we have developed PAM antagonists representing a pharmacologically novel class of antagonists.



Jan Jakubik PhD is an internationally recognized neuroscientist in the field of the neurochemistry of cholinergic signalling, molecular neuropharmacology of GPCRs and receptor theory. Among his major achievements are the conceptualization of signalling bias at the G-protein level, unravelling the role of cholesterol and neurosteroids in cholinergic signalling and discoveries of positive allosteric modulators of acetylcholine, allosteric agonists and long-acting muscarinic antagonists. He gained postdoctoral experience as a Fogarty Visiting Fellow at the National Institutes of Health, Bethesda, MD, USA, and as a Postdoctoral Associate in the Research in Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA. He has been the principal investigator of several grants of the Czech Science Foundation and participated in the 7th Frame Project of EU LipiDiDiet.

IPHYS contact person: Jan Jakubik,