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bioRxivNeurosciencePreprint

Development of photoactivatable drugs enables nicotinic optopharmacology

Sambashiva BanalaiD, Matthew C. ArviniD, Nicolas M. Bannon, Xiao-Tao Jin, Yong WangiD, Guiqing Zhao, John J. Marshall, Kyle R. Gee, David L. WokosiniD, Anis ContractoriD, Henry A. LesteriD, Yevgenia KozorovitskiyiD, Ryan M. DrenaniD, Luke D. LavisiD

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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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