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Photoactivatable drugs for nicotinic optopharmacology

Banala, Sambashiva and Arvin, Matthew C. and Bannon, Nicholas M. and Jin, Xiao-Tao and Macklin, John J. and Wang, Yong and Peng, Can and Zhao, Guiqing and Marshall, John J. and Gee, Kyle R. and Wokosin, David L. and Kim, Veronica J. and McIntosh, J. Michael and Contractor, Anis and Lester, Henry A. and Kozorovitskiy, Yevgenia and Drenan, Ryan M. and Lavis, Luke D. (2018) Photoactivatable drugs for nicotinic optopharmacology. Nature Methods, 15 (5). pp. 347-350. ISSN 1548-7091. PMCID PMC5923430.

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Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle Paper
Arvin, Matthew C.0000-0002-1744-2142
Wang, Yong0000-0001-7547-1542
Lester, Henry A.0000-0002-5470-5255
Kozorovitskiy, Yevgenia0000-0002-3710-1484
Drenan, Ryan M.0000-0002-8141-8577
Lavis, Luke D.0000-0002-0789-6343
Alternate Title:Development of photoactivatable drugs enables nicotinic optopharmacology
Additional Information:© 2018 Macmillan Publishers Limited, part of Springer Nature. Received: 26 September 2017; Accepted: 26 February 2018; Published: 26 March 2018. Data availability. The data that support the findings of this study, if not explicitly contained within the text, supplementary figures, or Supplementary Note 1, are available from the corresponding authors upon reasonable request. Source data for Figures 1 and 2 and Supplementary Figures 1–6 are available online. We thank members of the Drenan and Lavis laboratories for helpful advice and discussion, and T. Lerner (Northwestern University, Chicago, Illinois, USA) for contributing viral reagents. This work was supported by the Howard Hughes Medical Institute (to S.B., J.J.M., and L.D.L.), the US National Institutes of Health (NIH) (grants DA035942 and DA040626 to R.M.D., MH099114 to A.C., DA037161 to H.A.L., NS054850 to D.J. Surmeier, and GM103801 and GM48677 to J.M.M.), the PhRMA Foundation (fellowship to M.C.A.), the Arnold and Mabel Beckman Foundation (Beckman Young Investigator Award to Y.K.), the Bernice E. Bumpus Foundation (Early Career Innovation Award to Y.K.), the Rita Allen Foundation (to Y.K.), the Searle Scholars Program (to Y.K.), the Alfred P. Sloan Foundation (Sloan Research Fellowship to Y.K.), NINDS (grant NINDS F32 NS103243 to N.M.B.), the JPB Foundation, and Northwestern University. Author Contributions: R.M.D., M.C.A., H.A.L., S.B., K.R.G., and L.D.L. conceived the project. M.C.A., N.M.B., D.L.W., X.-T.J., J.J.M., Y.W., C.P., G.Z., V.J.K., J.J.M., A.C., Y.K., R.M.D., S.B., and L.D.L. planned and/or executed experiments. D.L.W., Y.K., J.M.M., and K.R.G. contributed essential reagents and expertise. R.M.D., M.C.A., S.B., and L.D.L. wrote the paper with input from all other authors. R.M.D. and L.D.L. supervised all aspects of the work. Competing interests: K.R.G. is an employee of Thermo Fisher Scientific and has stock options. All other authors declare no competing interests.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Bernice E. Bumpus FoundationUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
NIHF32 NS103243
Northwestern UniversityUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC5923430
Record Number:CaltechAUTHORS:20180402-095419703
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:85557
Deposited By: Tony Diaz
Deposited On:02 Apr 2018 17:30
Last Modified:09 Mar 2020 13:19

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