Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response.
Adam L. Halberstadt, Mark A. Geyer
Neuropharmacology February 1, 2014 DOI: 10.1016/j.neuropharm.2013.08.025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Interventions | 2C-I 25I-NBOMe 25I-NBMD M100 907 |
| Dose | 2C-I (1-10 mg/kg SC), 25I-NBOMe (0.1-1 mg/kg SC), 25I-NBMD (1-10 mg/kg SC) |
| Topics | LSD |
| Keywords | Psychedelic pharmacology 5-ht2a receptor activation Head twitch response |
| Citations | 113 |
| Key findings | 25I-NBOMe is 14-fold more potent than 2C-I in inducing the head twitch response via 5-HT(2A) receptor activation in mice. |
Abstract
N-benzyl substitution markedly enhances the affinity of phenethylamine hallucinogens at the 5-HT(2A) receptor. N-benzyl substituted derivatives of 2,5-dimethoxy-4-iodophenethylamine (2C-I), such as N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBOMe) and N-(2,3-methylenedioxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBMD), have appeared recently as designer drugs, but have not been characterized behaviorally. The head twitch response (HTR) is induced by 5-HT(2A) receptor activation in rats and mice, and is widely used as a behavioral proxy for hallucinogen effects in humans. Nevertheless, it is not clear whether phenethylamine hallucinogens reliably provoke this behavior. Hence, we investigated whether 2C-I, 25I-NBOMe and 25I-NBMD induce head twitches in C57BL/6J mice. The HTR was assessed using a head-mounted magnet and a magnetometer coil. 2C-I (1-10 mg/kg SC), 25I-NBOMe (0.1-1 mg/kg SC), and 25I-NBMD (1-10 mg/kg SC) induced the HTR. 25I-NBOMe displayed 14-fold higher potency than 2C-I, and the selective 5-HT(2A) antagonist M100,907 completely blocked the HTR induced by all three compounds. These findings show that phenethylamine hallucinogens induce the HTR by activating 5-HT(2A) receptors. Our results demonstrate that 25I-NBOMe is a highly potent derivative of 2C-I, confirming previous in vitro findings that N-benzyl substitution increases 5-HT(2A) affinity. Given the high potency and ease of synthesis of N-benzylphenethylamines, it is likely that the recreational use of these hallucinogens will become more widespread in the future.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 76
- 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
- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
- Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology December 1, 2015
- Legal highs: staying on top of the flood of novel psychoactive substances Therapeutic Advances in Psychopharmacology January 26, 2015
- Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential. Nature Communications December 15, 2023
and 71 more in the library
Cites 18
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- 25C-NBOMe--new potent hallucinogenic substance identified on the drug market. Forensic Science International April 10, 2013
- 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): clinical case with unique confirmatory testing. Journal of Medical Toxicology March 1, 2014
and 13 more in the library