Agonist-Trafficking and Hallucinogens
Current Medicinal Chemistry March 1, 2009 Javier Gonzalez-Maeso, Stuart Sealfon 74 citations
G protein-coupled receptors (GPCRs) are the most common target for therapeutic drugs. The traditional ternary complex model, where receptors shift between active and inactive states, has been revised because different agonists can activate distinct signaling pathways from the same receptor. This agonist-trafficking model proposes that agonists stabilize unique receptor conformations that preferentially trigger specific pathways. Hallucinogenic drugs like LSD, psilocybin, and mescaline, which act on serotonin 5-HT2A receptors, offer a useful system to study this phenomenon. Non-hallucinogenic chemicals like lisuride show similar in vitro activity at the same receptor but do not induce hallucinogenic effects, highlighting unresolved questions about how agonist-trafficking determines behavioral outcomes.