Effect of γ-mangostin through the inhibition of 5-hydroxytryptamine(2A) receptors in 5-fluoro-α-methyltryptamine-induced head-twitch responses of mice

1. Intracerebronventricular (i.c.v.) injection of γ-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-α-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-HT(1A)-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by γ-mangostin or ketanserin. 3. The locomotor activity stimulated by 5-FMT through the activation of α(1)-adrenoceptors did not alter in the presence of γ-mangostin. 4. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. γ-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation. 5. γ-Mangostin caused a concentration-dependent inhibition of the binding of [(3)H]-spiperone, a specific 5-HT(2A) receptor antagonist, to mouse brain membranes. 6. Kinetic analysis of the [(3)H]-spiperone binding revealed that γ-mangostin increased the K(d) value without affecting the B(max) value, indicating the mode of the competitive nature of the inhibition by γ-mangostin. 7. These results suggest that γ-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-HT(2A) receptors not by blocking the release of 5-HT from the central neurone. γ-Mangostin is a promising 5-HT(2A) receptor antagonist in the central nervous system