부산대학교 도서관

Abstract Rationale: Deramciclane fumarate is a new 5-HT[sub 2A] and 5-HT[sub 2C] receptor antagonist with putative anxiolytic effects. In the present study the binding of deramciclane to serotonin 5-HT[sub 2A] receptors in frontal cortex of healthy male volunteers was studied using [[sup 11]C]-N-methyl spiperone ([[sup 11]C]-NMSP) and positron emission tomography. Methods: The receptor occupancy percentage was assessed by the means of inhibition of [[sup 11]C]-NMSP from the 5-HT[sub 2A] receptors in the frontal cortex. Single oral doses of 20, 50 and 150 mg deramciclane were given to three subjects at each dose level (total n = 9). The receptor occupancy was measured before deramciclane and at 3 and 6 h post-dosing except at the 20 mg dose level where only the 3-h measurement was done. The occupancy percentage was calculated with the ratio method using cerebellum as a reference area. Results: Deramciclane inhibited [[sup 11]C]-NMSP binding dose and concentration dependently. However, deramasciclane inhibited maximally only 52% of the [[sup 11]C]-NMSP binding in the frontal cortex, indicating a non-5-HT[sub 2A] receptor binding component of this radioligand in frontal cortex. On average, specific [[sup 11]C]-NMSP binding cerebellum ratios below 0.355 were not possible to achieve in this population. The 52% inhibition was regarded to represent near 100% 5-HT[sub 2A] receptor occupancy. The 50 and 90% receptor occupancies were reached at deramciclane plasma concentrations of 21 ng/ml and 70 ng/ml, respectively. Conclusions: Deramciclane penetrates the blood-brain barrier in humans. Deramciclane binds to the 5-HT[sub 2A] receptors in the frontal cortex in a saturable manner in vivo. Consequently, the increase in deramciclane concentration in plasma above 70 ng/ml will not result in... [ABSTRACT FROM AUTHOR]