Does a CNO analog that does not cross the blood–brain barrier exist?

I am looking for a CNO analog that does not cross the blood–brain barrier (BBB). Does it exists?

This will be beneficial for any PNS studies in which activation of DREADDs expressed in the CNS is not desirable.

For instance, the use of Cx3cr1-cre mice with DREADDs loxP will result having DREADDs in microglia and macrophages, but a CNO that do not cross BBB will allow to dissect the unique contributions of macrophages without affecting microglia.

@tberta - Good question.

I asked this question a few months ago, and at the time a CNO analog that remained just in the periphery did not exist. I agree that such a compound would be powerful.

An SAR approach to develop a CNS-impermeant ligand in the same vein as this paper would be the way foward probably.

Maybe if enough people are interested, there will one day be such a tool.