AGONIST ACTIVITY OF LSD AND LISURIDE AT CLONED 5HT(2A) AND 5HT(2C) RECEPTORS

Evidence from studies with phenylisopropylamine hallucinogens indicate s that the 5HT(2A) receptor is the likely target for the initiation of events leading to hallucinogenic activity associated with LSD and rel ated drugs. Recently, lisuride (a purported non-hallucinogenic congene r of LSD) was reported to be a potent antagonist at the 5HT(2C) recept or and an agonist at the 5HT(2A) receptor. LSD exhibited agonist activ ity at both receptors, These data were interpreted as indicating that the 5HT(2C) receptor might be the initiating site of action for halluc inogens. To test this hypothesis, recombinant cells expressing 5HT(2A) and 5HT(2C) receptors were used to determine the actions of LSD and l isuride, LSD and lisuride were potent partial agonists at 5HT(2A) rece ptors with EC50 values of 7.2 nM and 17 nM, respectively. Also, LSD an d lisuride were partial agonists at 5HT(2C) receptors with EC50 values of 27 nM and 94 nM, respectively. We conclude that lisuride and LSD h ave similar actions at 5HT(2A) and 5HT(2C) receptors in recombinant ce lls. As agonist activity at brain 5HT(2A) receptors has been associate d with hallucinogenic acitivity, these results indicate that lisuride may possess hallucinogenic activity, although the psychopharmacologica l effects of lisuride appear to be different from the hallucinogenic e ffects of LSD.