Compositions and methods for controlling neuronal excitation

摘要

Embodiments of the technology described herein relate, at least in part, to methods of modulating the activity of a neuron by contacting the neuron with a photo-sensitive TrpA1 agonist and then illuminating the neuron with electromagnetic radiation. Also described herein are photo-sensitive TrpA1 agonists.

主权项

1. A method of modulating the activity of a neuron, the method comprising;
a) contacting the neuron with a compound of formula Ia or Ib: wherein R11 is hydrogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)RB; —CO2RB; or —C(RB)3; wherein each occurrence of RB is independently hydrogen; halogen; a protecting group; aliphatic; heteroaliphatic; acyl; aryl moiety; heteroaryl; hydroxyl; aloxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; heteroarylthioxy; or alkylhalo; R12, R13, and R14, are independently hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)RB; —CO2RB; -; —CN; —SCN; —SRB; —SORB; —SO2RB; —NO2; —N(RB)2; —NHC(O)RB; or —C(RB)3; wherein each occurrence of RB is independently hydrogen; halogen; a protecting group; aliphatic; heteroaliphatic; acyl; aryl moiety; heteroaryl; hydroxyl; aloxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; heteroarylthioxy; or alkylhalo; R15 is hydrogen; Y1 is O; Y2 is S; X1 is NH; X2 is NH or S; and b) exposing the neuron to electromagnetic radiation comprising a wavelength of from about 300 nm to about 700 nm.