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 Ki value of LS-121 was 6.08 x 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.
Nabeshima
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Hiramatsu
M
M
Niwa
K
K
Fuji
K
K
Kameyama
T
T
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D001665:Binding Sites; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007650:Ketanserin / Q000378:metabolism*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D009257:Nafronyl / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D014018:Tissue Distribution
D011985:Receptors, Serotonin; D016713:Ritanserin; D009257:Nafronyl; D007650:Ketanserin; D010293:Pargyline; D006916:5-Hydroxytryptophan; D008784:Methysergide