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Matsumoto, K. et al.

Matsumoto, Morishige, Murakami, Tohda, Takayama, Sakakibara, Watanabe,

Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the brain: behavioural and electrophysiological studies.

Isorhynchophylline is a major oxindole alkaloid found in Uncaria species which have long been used in traditional Chinese medicine. Here, we investigated the effects of isorhynchophylline and isorhynchophylline-related alkaloids on 5-hydroxytryptamine (5-HT) receptor- mediated behavioural responses in mice and 5-HT-evoked current responses in Xenopus oocytes expressing 5-HT2A or 5-HT2C receptors. Isorhynchophylline dose-dependently inhibited 5-HT2A receptor- mediated head-twitch but not 5-HT1A receptor-mediated head-weaving responses evoked by 5-methoxy-N,N-dimethyltryptamine. Pretreatment with reserpine, a monoamine-depleting agent, enhanced the head-twitching, but did not influence the effect of isorhynchophylline on the behavioural response. Isocorynoxeine, an isorhynchophylline-related alkaloid in which the configuration of the oxindole moiety is the same as in isorhynchophylline, also reduced the head-twitch response in reserpinized mice over the same dose range as isorhynchophylline, while both rhynchophylline and corynoxeine, stereoisomers of isorhynchophylline and isocorynoxeine, did not. None of the alkaloids tested had an effect on meta-chlorophenylpiperazine-induced hypolocomotion, a 5-HT2C receptor-mediated behavioural response. In experiments in vitro, isorhynchophylline and isocorynoxeine dose-dependently and competitively inhibited 5-HT-evoked currents in Xenopus oocytes expressing 5-HT2A receptors, but had less of a suppressive effect on those in oocytes expressing 5-HT2C receptors. These results indicate that isorhynchophylline and isocorynoxeine preferentially suppress 5-HT2A receptor function in the brain probably via a competitive antagonism at 5-HT2A receptor sites and that the configuration of the oxindole moiety of isorhynchophylline is essential for their antagonistic activity at the 5-HT2A receptor.[1]

References

Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the brain: behavioural and electrophysiological studies. Matsumoto, K., Morishige, R., Murakami, Y., Tohda, M., Takayama, H., Sakakibara, I., Watanabe, H. Eur. J. Pharmacol. (2005) [Pubmed]

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