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Biological Activity:

AA92593 is a potent and selective small molecule antagonist of melanopsin-mediated photo-transduction (IC₅₀ ~160 nM). It inhibits melanopsin (opsinamides) by competing with retinal binding to melanopsin, and inhibits its function without affecting rod- and cone-mediated responses. In vivo administration of AA92593 to mice specifically and reversibly modified melanopsin-dependent light responses, including the pupillary light reflex and light aversion. Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image-forming photic responses. The discovery of AA92593 raises the prospect of therapeutic control of the melanopsin photo-transduction system to regulate light-dependent behavior and remediate pathological conditions.

How to Use:

In vitro:  AA92593 was used at 10 µM final concentration in various in vitro assays.

In vivo: AA92593 was dosed intraperitoneally 30 mg/kg 20 min before PLR measurement attenuated pupil constriction in response to light (10¹³ ph cm^-2 s^-1) by ~50% in ***** rd mice. 

Reference:

•  1. Jones KA, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. (2013) Nat Chem Biol. 9(10):630-5.