Small-molecule antagonists of melanopsin-mediated phototransduction

Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T.E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image-forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several central nervous system responses, including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. New sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod- and cone-mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses, including the pupillary light reflex and light aversion. The discovery of opsinamides raises the prospect of therapeutic control of the melanopsin phototransduction system to regulate light-dependent behavior and remediate pathological conditions.

Original languageEnglish (US)
Pages (from-to)630-635
Number of pages6
JournalNature Chemical Biology
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Light Signal Transduction
Light
Pupillary Reflex
Photophobia
Vertebrate Photoreceptor Cells
Retinal Ganglion Cells
Sulfonamides
Circadian Rhythm
melanopsin
Sleep
Central Nervous System
Pharmacology

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Jones, K. A., Hatori, M., Mure, L. S., Bramley, J. R., Artymyshyn, R., Hong, S. P., ... Panda, S. (2013). Small-molecule antagonists of melanopsin-mediated phototransduction. Nature Chemical Biology, 9(10), 630-635. https://doi.org/10.1038/nchembio.1333

Small-molecule antagonists of melanopsin-mediated phototransduction. / Jones, Kenneth A.; Hatori, Megumi; Mure, Ludovic S.; Bramley, Jayne R.; Artymyshyn, Roman; Hong, Sang Phyo; Marzabadi, Mohammad; Zhong, Huailing; Sprouse, Jeffrey; Zhu, Quansheng; Hartwick, Andrew T.E.; Sollars, Patricia J.; Pickard, Gary E.; Panda, Satchidananda.

In: Nature Chemical Biology, Vol. 9, No. 10, 01.10.2013, p. 630-635.

Research output: Contribution to journalArticle

Jones, KA, Hatori, M, Mure, LS, Bramley, JR, Artymyshyn, R, Hong, SP, Marzabadi, M, Zhong, H, Sprouse, J, Zhu, Q, Hartwick, ATE, Sollars, PJ, Pickard, GE & Panda, S 2013, 'Small-molecule antagonists of melanopsin-mediated phototransduction', Nature Chemical Biology, vol. 9, no. 10, pp. 630-635. https://doi.org/10.1038/nchembio.1333
Jones KA, Hatori M, Mure LS, Bramley JR, Artymyshyn R, Hong SP et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nature Chemical Biology. 2013 Oct 1;9(10):630-635. https://doi.org/10.1038/nchembio.1333
Jones, Kenneth A. ; Hatori, Megumi ; Mure, Ludovic S. ; Bramley, Jayne R. ; Artymyshyn, Roman ; Hong, Sang Phyo ; Marzabadi, Mohammad ; Zhong, Huailing ; Sprouse, Jeffrey ; Zhu, Quansheng ; Hartwick, Andrew T.E. ; Sollars, Patricia J. ; Pickard, Gary E. ; Panda, Satchidananda. / Small-molecule antagonists of melanopsin-mediated phototransduction. In: Nature Chemical Biology. 2013 ; Vol. 9, No. 10. pp. 630-635.
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