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-HT receptor pharmacological tool, or none of the above?

The development of 5-HT 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-HT receptors. Nonetheless, the ability of drugs to stimulate 5-HT receptors is not necessarily associated with psychedelic experience and the hallucinogenic properties are still not understood. Several studies have increased interest in stimulating 5-HT 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-HT 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-HT receptors. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.