PhytoScience - Science 
Anti-tremor (Parkinson) - Invivo
Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice.
Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y.
Department of Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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 alpha1-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 [3H]-spiperone, a specific 5-HT2A receptor antagonist, to mouse brain membranes.
6. Kinetic analysis of the [3H]-spiperone binding revealed that gamma-mangostin increased the Kd value without affecting the Bmax 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.
PMID: 9535013 [PubMed - indexed for MEDLINE]