2009/02/13 by Dominique Fontanilla, Molly Johannessen, Abdol R. Hajipour +3 · 4 citations
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Pharmacological Receptor Mechanisms and Effects #Receptor Mechanisms and Signaling #Neuroscience and Neuropharmacology Research
paper · doi:10.1126/science.1166127
openalex publication_date 2009/02/13 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/02
The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.