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.
J Neural Transm (Vienna)
September 12, 2009
Nicholas V. Cozzi, Anupama Gopalakrishnan, Lyndsey L. Anderson et al.
144 citations
N,N-dimethyltryptamine (DMT) and related tryptamines inhibit serotonin transport at the serotonin transporter (SERT) and vesicle monoamine transporter (VMAT2) with varying potencies. DMT, MIPT, DPT, and DIPT inhibited serotonin uptake at SERT with Ki values of 4.00, 8.88, 0.594, and 2.32 µM, respectively. At VMAT2, inhibition was weaker, with Ki values of 93, 20, 19, and 19 µM. The tryptamines were poor inhibitors of radioligand binding to these transporters, yielding high binding-to-uptake ratios. This pattern suggests the tryptamines act as transporter substrates rather than uptake blockers, indicating separate substrate and inhibitor binding sites. The transporters may concentrate tryptamines inside neurons for sigma-1 receptor activation and potential release as transmitters.