The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.
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.
Fontanilla
Dominique
D
Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Johannessen
Molly
M
Hajipour
Abdol R
AR
Cozzi
Nicholas V
NV
Jackson
Meyer B
MB
Ruoho
Arnold E
AE
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006168:Guinea Pigs; D006213:Hallucinogens / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D004130:N,N-Dimethyltryptamine / Q000378:metabolism*; D051381:Rats; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014363:Tryptamines / Q000378:metabolism; D000097605:Sigma-1 Receptor
D006213:Hallucinogens; D008024:Ligands; D004130:N,N-Dimethyltryptamine; D017480:Receptors, sigma; D014363:Tryptamines; D000097605:Sigma-1 Receptor; C030820:tryptamine; C035668:N-methyltryptamine