Effect of naftidrofuryl oxalate on 5-HT₂ receptors in mouse brain: evaluation based on quantitative autoradiography and head-twitch response

The effects of naftidrofuryl oxalate (LS-121) on 5-HT₂ receptors in the brain were assessed in mice on the basis of quantitative autoradiography and head-twitch responses. LS-121 inhibited [³H]ketanserin (2 nM) binding in all brain areas assayed in which there were 5-HT₂ receptors, such as the frontal cortex, cingulate cortex, parietal cortex, occipital cortex, temporal cortex, nucleus accumbens, caudate-putamen, olfactory tubercle and hippocampus. In the frontal cortex, which has the highest density of 5-HT₂ receptors, the K_i value of LS-121 was 6.08 × 10^-8 M. The inhibitory potencies of methysergide and ritanserin for 5-HT₂ receptors were about 16- and 60-fold stronger, respectively, than that of LS-121. Moreover, in behavioral studies, LS-121 (12.5-50 mg/kg i.p.) produced dose-dependent and significant inhibitory effects on head twitches induced by 5-hydroxytryptophan (5-HTP) plus pargyline, which is a 5-HT₂ receptor-dependent behavior in mice. These results suggest that LS-121 inhibits 5-HTP plus pargyline-induced head twitches by blocking 5-HT₂ receptors.