The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator
Science February 13, 2009 Dominique Fontanilla, Molly Johannessen, Abdol R. Hajipour et al. 528 citations
The sigma-1 receptor, once mistaken for an opioid receptor, binds many synthetic compounds but not opioid peptides and is now considered an orphan receptor. Its pharmacophore includes an alkylamine core also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion channels in both native cardiac myocytes and heterologous cells expressing sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.