Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice.
We investigated the effects of mitragynine, a major alkaloid isolated from the leaves of Mitragyna speciosa Korth (Rubiaceae), on the 5-HT2A receptor-mediated head-twitch response in mice. Intraperitoneal injection of mitragynine (5-30 mg/kg), as well as intraperitoneal injection of 5-HT2A receptor antagonist ritanserin, inhibited the 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT: 16 mg/kg, IP)-induced head-twitch response in a dose-dependent manner. In contrast, mitragynine affected neither head-weaving caused by 5-MeO-DMT, nor drug-free spontaneous motor activity. Pretreatment of mice with reserpine (5 mg/kg, IP), p-chlorophenylalanine (p-CPA, 300 mg/kg x 3 times, IP), or 6-hydroxydopamine (6-OHDA, 50 micrograms/mouse, ICV) plus nomifensine (5 mg/kg, IP) did not change the suppressant effect of mitragynine on the head-twitch response caused by 5-MeO-DMT. On the other hand, the alpha 2-adrenoceptor antagonists yohimbine (0.5 mg/kg, IP), and idazoxan (0.2 mg/kg, IP), significantly attenuated the suppressant effect of mitragynine. Lesion of central noradrenergic systems by 6-OHDA plus nomifensine did not alter the effect of idazoxan (0.2 mg/kg) on mitragynine-induced suppression of the head-twitch response. These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine.
Matsumoto
K
K
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Mizowaki
M
M
Takayama
H
H
Sakai
S
S
Aimi
N
N
Watanabe
H
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004353:Drug Evaluation, Preclinical; D019416:Head Movements / Q000187:drug effects*; D008297:Male; D008732:Methoxydimethyltryptamines / Q000037:antagonists & inhibitors*; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D008732:Methoxydimethyltryptamines; D046948:Secologanin Tryptamine Alkaloids; D012702:Serotonin Antagonists; D012110:Reserpine; C001801:mitragynine