Suppressive effect of nantenine, isolated from Nandina domestica Thunberg, on the 5-hydroxy-L-tryptophan plus clorgyline-induced head-twitch response in mice.
We investigated the effects of nantenine (9,10-Methylenedioxy-1,2 dimethoxyaporphine), a major alkaloid isolated from the fruit of Nandina domestica Thunb (Berberidaceae), on the 5-HT2A receptor-mediated head-twitch response (HTR) in mice. Intraperitoneal (i.p.) injection of nantenine (13.3, 20 and 30 mg/kg) as well as the 5-HT2A receptor antagonist ketanserin (0.0625, 0.25 and 1 mg/kg) inhibited the 5-hydroxy-L-tryptophan (l-5-HTP; 75 mg/kg, i.p.) plus monoamine oxidase inhibitor, clorgyline (1 mg/kg, i.p.)-induced HTR in a dose-dependent manner. In contrast, neither l-5-HTP plus clorgyline nor 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 5 microg/mouse, i.c.v.)-induced head weaving was affected by nantenine or ketanserin. Furthermore, neither nantenine (up to 30 mg/kg) nor ketanserin (up to 1 mg/kg) affect on the locomotor activity. In the receptor binding studies, nantenine showed affinity to the 5-HT2A receptors (Ki = 0.4 microM), while it had less affinity toward alpha1-adrenergic (Ki = 2.1 microM) and D2-dopaminergic (Ki = 1.7 microM) receptors of the mouse brain. These results suggest that nantenine inhibits l-5-HTP plus clorgyline-induced head- twitch response by blocking 5-HT2A receptors in the central nervous system.
Indra
Bachtiar
B
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Tadano
Takeshi
T
Nakagawasai
Osamu
O
Arai
Yuichiro
Y
Yasuhara
Hajime
H
Ohizumi
Yasushi
Y
Kisara
Kensuke
K
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001060:Aporphines / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology*; D005638:Fruit; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009069:Movement Disorders / Q000188:drug therapy*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D001060:Aporphines; D008996:Monoamine Oxidase Inhibitors; D010936:Plant Extracts; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D006916:5-Hydroxytryptophan; D003010:Clorgyline; C041615:nantenine