Development of photoactivatable drugs enables nicotinic optopharmacology

Sambashiva Banala; Matthew C. Arvin; Nicolas M. Bannon; Xiao-Tao Jin; Yong Wang; Guiqing Zhao; John J. Marshall; Kyle R. Gee; David L. Wokosin; Anis Contractor; Henry A. Lester; Yevgenia Kozorovitskiy; Ryan M. Drenan; Luke D. Lavis

doi:10.1101/260232

NeurosciencebioRxivFeb 5, 2018

Preprint

Development of photoactivatable drugs enables nicotinic optopharmacology

Sambashiva Banala iD, Matthew C. Arvin iD, Nicolas M. Bannon, Xiao-Tao Jin, Yong Wang iD, Guiqing Zhao, John J. Marshall, Kyle R. Gee, David L. Wokosin iD, Anis Contractor iD, Henry A. Lester iD, Yevgenia Kozorovitskiy iD, Ryan M. Drenan iD, Luke D. Lavis iD

Abstract

Photoactivatable ( caged) pharmacological agents have revolutionized neuroscience but the palette of available ligands is limited. We describe a general method for caging tertiary amines using an unconventional quaternary ammonium linkage that is chemically stable and elicits a desirable red-shift in activation wavelength. A photoactivatable nicotine (PA-Nic) prepared using this strategy could be uncaged via 1- or 2-photon excitation, making it useful for optopharmacology experiments to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales.

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