In behaving animals chemogenetics enables chemical control over cell populations. But, existing agonists show selectivity or potency. There is also a demand to get chemogenetic systems compatible with both research and therapeutic applications that are human. We synthesized subnanomolar-potency agonists, known as uPSEMs, with higher selectivity for the receptors. UPSEMs and their receptors have been characterized in brains of mice and a rhesus monkey by in vivo electrophysiology, calcium imaging, positron emission tomography efficacy testing, and receptor counterscreening. This stage of receptors and selective ultrapotent agonists enables possible clinical and research uses of chemogenetics.