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Pharmacology and Neurotoxicity of 5-MeO-DIPT

Krystyna Gołembiowska

Handbook of Neurotoxicity 2021 DOI: 10.1007/978-3-030-71519-9_207-1 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal study Peer reviewed
Population Adolescent rats
Intervention 5-MeO-DIPT
Dose 2.5 mg/kg × 8
Topics 5-MeO-DMT
Keywords 5-MEO-Dipt Neurotransmitters Dna damage Adolescence
Key points Repeated intermittent administration of 5-MeO-DIPT during adolescence in rats caused oxidative DNA damage in the cortex, altered neurotransmitter responses, and impaired long-term memory and cognitive flexibility.

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.

Comparable studies

Other preclinical and animal studies on 5-MeO-DMT, most cited first.

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