Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats.
William E Fantegrossi, A W Harrington, C L Kiessel, Justin R Eckler, R A Rabin, Jerrold C Winter, Andrew Coop, K C Rice, James H Woods
Pharmacology, Biochemistry, and Behavior 2006 DOI: 10.1016/j.pbb.2005.12.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice and rats |
| Interventions | 5-MeO-DIPT N N-DMT M100907 WAY-100635 LSD |
| Topics | 5-MeO-DMT |
| Citations | 144 |
| Key points | 5-MeO-DIPT acts primarily through the 5-HT2A receptor to produce its behavioral effects in rodents, despite having higher in vitro affinity for the 5-HT1A receptor. |
Abstract
Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT 1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT 2A and 5-HT 2C receptors, but much higher affinity for 5-HT 1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT 2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT 1A receptor.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 68
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
and 63 more in the library
Cites 17
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