Aniracetam attenuates the 5-HT2 receptor-mediated head-twitch response in rodents as a hallucination model

The effects of aniracetam on the head-twitch response (HTR) induced by 5-hydroxy-L-tryptophan (5-HTP) and (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) as a model of hallucination were examined in rodents. 1) Aniracetam produced a dose-related (30, 100, and 300 mg/kg po) reduction in the frequency of HTR induced by 5-HTP at 300 mg/kg ip in mice, p-Anisic acid (300 mg/kg po), one of the main metabolites of aniracetam, inhibited the HTR as the intact drug did. Other nootropics, tacrine (10 mg/kg po) and idebenone (100 mg/kg po), but not propentofylline, also reduced HTR. Ritanserin (0.1 and 1 mg/kg po) and cyproheptadine (1 mg/kg po) markedly antagonized it, but ondansetron (1 and 10 mg/kg po) and metoclopramide (1 mg/kg po) did not. Although scopolamine alone (1 mg/kg sc) produced no HTR, it, but not butylscopolamine, potentiated the HTR induced by 5-HTP at the minimum effective dose (200 mg/kg ip). The potentiation of the HTR induced by the combined 5-HTP and scopolamine was inhibited by aniracetam (100 mg/kg po), tacrine (10 mg/kg po), and ritanserin (1 mg/kg po). 2) The DOI (1 mg/kg sc)-induced HTR was inhibited by aniracetam (30 and 100 mg/kg po), tacrine (3 mg/kg po), and ritanserin (1 mg/kg po). 3) Aniracetam and its metabolites had no effect on the 5-HT2 and 5-HT3 binding in vitro. These results indicate that clinical efficacy of aniracetam on delirium associated with the sequelae of cerebrovascular diseases may be partly due to the indirect regulation of serotonergic functions via an inhibitory cholinergic mechanism. (C) 1998 Wiley-Liss, Inc.