Pharmacology and Neurotoxicity of 5-MeO-DIPT

The psychedelic drug 5-MeO-DIPT (street name 'foxy') acts as a serotonin transporter inhibitor and agonist at serotonin receptors, producing hallucinogenic effects and increasing release of dopamine, serotonin, and glutamate in rat brain regions. In cell lines, it shows potent cytotoxicity. Repeated intermittent doses during adolescence in rats reduced the response to a subsequent challenge dose in some brain regions and caused oxidative DNA damage in the cortex. Exposed rats showed stronger neurotransmitter responses to MDMA and performed worse on cognitive tasks, with impairments in long-term memory and cognitive flexibility, suggesting that adolescent exposure may lead to neurological problems in adulthood.

Study at a glance

Abstract

Psychedelics are drugs that alter consciousness and affect human psyche. 5-Methoxy- N,N -diisopropyltryptamine (5-MeO-DIPT) emerged in the recreational drug market with the street name “foxy” and has been increasingly used as a substitute for methylenedioxymethamphetamine (MDMA) Methylenedioxymethamphetamine (MDMA) . 5-MeO-DIPT is a competitive inhibitor of the serotonin (5-HT) transporter (SERT), having lower affinity for the dopamine (DA) transporter (DAT) but with high affinity for 5-HT2A, 5-HT2C, and 5-HT1A receptors. As a 5-HT2A receptor agonist, 5-MeO-DIPT produces hallucinogenic effect in mice and rats and increases in vivo release of DA, 5-HT, and glutamate in rat striatum, nucleus accumbens, and frontal cortex. The potent cytotoxic effect of 5-MeO-DIPT was demonstrated in COS-7 cells and in SH-SY5Y and Hep G2 cell lines . Repeated-intermittent 5-MeO-DIPT administration (2.5 mg/kg × 8) in adolescence decreased response to a challenge dose of 5-MeO-DIPT in release of DA, 5-HT, and glutamate in some regions of the rat brain. Furthermore, oxidative DNA damage was observed in the rat cortex. In rats exposed to 5-MeO-DIPT during adolescence, response of DA, 5-HT, and glutamate neurons in the frontal cortex to a challenge dose of MDMA was stronger in comparison with the saline group. 5-MeO-DIPT disturbed animal performance in certain cognitive tasks, while exposure of adolescent rats to repeated-intermittent doses of 5-MeO-DIPT produced impairment of long-term memory or cognitive flexibility in the serial pattern learning test. Abnormalities seen after exposure to 5-MeO-DIPT during adolescence suggest that developmental changes may cause neurological problems in adult life.