5-Methoxy-N,N-diisopropyltryptamine (Foxy), a selective and high affinity inhibitor of serotonin transporter.

5-MeO-DIPT, a synthetic hallucinogenic tryptamine, acts as a competitive inhibitor of the serotonin transporter (SERT), blocking serotonin uptake with high affinity and at concentrations similar to cocaine. It does not stimulate reverse transport of serotonin through SERT, and it prevents the serotonin-releasing action of methamphetamine. At high concentrations, the compound is toxic to cells, but this toxicity is not influenced by SERT expression. These findings clarify the serotonergic mechanism of 5-MeO-DIPT.

Study at a glance

Abstract

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a synthetic orally active hallucinogenic tryptamine derivative, known also as Foxy or Foxy methoxy. However, few studies have examined its effects in vitro. In the present study, we investigated the actions of 5-MeO-DIPT against monoamine neurotransmitter transporters, including the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), using COS-7 cells heterologously expressing these transporters and rat brain synaptosomes. 5-MeO-DIPT specifically inhibited the uptake of [3H]serotonin (5-HT) by the SERT-expressing COS-7 cells and rat striatal synaptosomes in a high affinity manner at concentrations similar to those for cocaine. The effect was reversible and competitive. 5-MeO-DIPT failed to stimulate reverse transport of [3H]5-HT through SERT, while it prevented the releasing action of methamphetamine. 5-MeO-DIPT induced cell toxicity at high concentrations in COS-7 cells, and it was not influenced by the expression of SERT. These results demonstrated that 5-MeO-DIPT acts as a competitive SERT inhibitor and has an inability to cause reverse transport, underlying its serotonergic actions.