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.British Journal of Pharmacology (1998) 123 , 855–862; doi: 10.1038/sj.bjp.0701695