TCB-2 [(7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine]: A hallucinogenic drug, a selective 5-HT2A receptor pharmacological tool, or none of the above?
Giuseppe Di Giovanni, Philippe De Deurwaerdère
Neuropharmacology November 2018 DOI: 10.1016/j.neuropharm.2017.10.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Biased agonists Hallucinogens Rat Schizophrenia Mpfc |
| Key findings | Argues that the suspected hallucinogenic properties of TCB-2 cannot be firmly established, because its pharmacological profile is unknown and it is likely not selective at 5-HT2A receptors. Notes that TCB-2 preferentially stimulates the phospholipase C rather than phospholipase A2 pathway, unlike several hallucinogenic drugs, and that 5-HT2A stimulation is not necessarily associated with psychedelic experience. |
Abstract
The development of 5-HT2A receptor agonists has been considerably marginalized since the demonstration that the tryptaminergic drugs, LSD and psilocybin, or the phenylakylamine drugs, mescaline and DOI, exert their hallucinogenic properties via the stimulation of 5-HT2A receptors. Nonetheless, the ability of drugs to stimulate 5-HT2A receptors is not necessarily associated with psychedelic experience and the hallucinogenic properties are still not understood. Several studies have increased interest in stimulating 5-HT2A receptors in various CNS diseases. (7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine (TCB-2) which was synthetized in 2006 presents a high affinity with human and rat 5-HT2A receptors. Its main feature of interest is that it preferentially stimulates the phospholipase C and not phospholipase A2 pathway, which is at variance with several hallucinogenic drugs. Preference for TCB-2 has increased in preclinical studies and it exhibits subtle differences compared to DOI or LSD in some molecular, cellular and behavioral studies. The purpose of this review is to take a position on the use of TCB-2 as a pharmacological tool. A careful reading of the literature has revealed that the suspected hallucinogenic properties of TCB-2 cannot firmly be ascertained while its pharmacological profile is unknown and likely not selective at 5-HT2A receptors. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
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- Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice. Pharmacology, Biochemistry, and Behavior February 1, 2024
- Exploring the therapeutic potential of psychedelics: Fear extinction mechanisms and amygdala modulation Psychedelics August 9, 2024
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