Complanadine A, a selective agonist for the Mas-related G protein-coupled receptor X2

The first biological target for the natural product complanadine A has been determined. The pseudosymmetric alkaloid functions as a selective agonist for the Mas-related G protein-coupled receptor X2 (MrgprX2), a G protein-coupled receptor that is highly expressed in neurons. Given the potential of MrgprX2 to function as a modulator of pain, complanadine A represents a new chemical probe to selectively interrogate the physiological function of MrgprX2 as well as a potential lead for the development of antihyperalgesics for the treatment of persistent pain. While complanadine A possess agonistic activity the related natural product lycodine, representing half of complanadine A, lacks activity providing a cursory description of the structural requirements for agonistic activity.