Effect of γ-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-α-methyltryptamine-induced head-twitch responses of mice

1 Intracerebronventricular (i.c.v.) injection of gamma-mangostin (10-40 nmol/mouse), a major compound of the fruit hull of Garcinia mangostana Lin., like ketanserin (10, 20 nmol/mouse, i.c.v.) inhibited 5-fluoro-alpha-methyltryptamine (5-FMT) (45 mg kg(-1), i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (a 5-hydroxytryptamine (5-HT)-uptake inhibitor). 2 Neither the 5-FMT- nor the 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by gamma-mangostin or ketanserin. 3 The locomotor activity stimulated by 5-FMT through the activation of alpha(1)-adrenoceptors did not alter in the presence of gamma-mangostin. 4 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. gamma-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation. 5 gamma-Mangostin caused a concentration-dependent inhibition of the binding of [H-3]-spiperone, a specific 5-HT2A receptor antagonist, to mouse brain membranes. 6 Kinetic analysis of the [H-3]-spiperone binding revealed that gamma-mangostin increased the K-d value without affecting the B-max value, indicating the mode of the competitive nature of the inhibition by gamma-mangostin. 7 These results suggest that gamma-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-HT2A receptors not by blocking the release of 5-HT from the central neurone. gamma-Mangostin is a promising 5-HT2A receptor antagonist in the central nervous system.