The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

被引：419

作者：

Fontanilla, Dominique ^{[1
]}

Johannessen, Molly ^{[2
]}

Hajipour, Abdol R. ^{[3
]}

Cozzi, Nicholas V. ^{[1
]}

Jackson, Meyer B. ^{[2
]}

Ruoho, Arnold E. ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pharmacol, Madison, WI 53706 USA

[2] Univ Wisconsin, Sch Med & Publ Hlth, Dept Physiol, Madison, WI 53706 USA

[3] Isfahan Univ Technol, Pharmaceut Res Lab, Dept Chem, Esfahan 84156, Iran

来源：

SCIENCE | 2009年 / 323卷 / 5916期

关键词：

TRACE AMINES; BINDING-SITE; IN-VIVO; CHANNELS; IDENTIFICATION; TRYPTAMINES; MODULATION; TERMINALS; LIGANDS; MOUSE;

D O I：

10.1126/science.1166127

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：934 / 937

页数：4

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