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ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist.

C Acuña-castillo, C Scorza, M Reyes-parada, B K Cassels, J P Huidobro-toro

Life sciences November 17, 2000 Peer reviewed DOI: 10.1016/s0024-3205(00)00906-1 via PubMed

Summary

ALEPH-2 acts as a partial agonist at the 5-HT2A receptor with potency comparable to 5-HT, while it is a full agonist at the 5-HT2C receptor, being about 15 times less potent than 5-HT. Additionally, pre-application of ritanserin at 1 microM effectively blocked responses from both 5-HT and ALEPH-2, although the 5-HT2A receptor showed greater sensitivity to this blockade compared to the 5-HT2C receptor.

Study at a glance

Population Xenopus laevis oocytes
Key finding ALEPH-2 is a partial agonist on the 5-HT2A receptor and a full agonist on the 5-HT2C receptor, with significantly different potencies compared to 5-HT.

Abstract

To assess the pharmacodynamic profile of ALEPH-2, a phenylisopropylamine derivative with alleged anxiolytic and hallucinogenic properties, Xenopus laevis oocytes were microinjected with either of the rat cRNA for the 5-HT2A or the 5-HT2C receptor. Concentration-response curves were obtained following the exposure of the oocytes to varying concentrations of either ALEPH-2 or 5-hydroxytryptamine (5-HT) for 10 s. ALEPH-2 is a partial agonist on the 5-HT2A receptor with a similar potency to 5-HT. In contrast, ALEPH-2 is a full 5-HT2C receptor agonist and is about 15-fold less potent than 5-HT. Pre-application of 1 microM ritanserin antagonized the responses induced by 5-HT and ALEPH-2 to the same extent; however, the 5-HT2A receptor is more sensitive to ritanserin blockade than the 5-HT2C receptor.

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