Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-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 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.
Chairungsrilerd
N
N
Department of Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Furukawa
K
K
Tadano
T
T
Kisara
K
K
Ohizumi
Y
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D007276:Injections, Intraventricular; D007295:Inositol Phosphates / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013134:Spiperone / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology*; D014966:Xanthenes / Q000008:administration & dosage / Q000494:pharmacology*; D044004:Xanthones
D007295:Inositol Phosphates; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014363:Tryptamines; D014966:Xanthenes; D044004:Xanthones; D013134:Spiperone; C051101:5-fluoro-alpha-methyltryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C021053:mangostin