Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats

Feb 8, 2006Pharmacology, biochemistry, and behavior

Hallucinogen-like effects of 5-methoxy-N,N-diisopropyltryptamine in mice and rats

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Abstract

5-MeO-DIPT induced head twitch responses in mice, which were potently antagonized by M100907.

5-MeO-DIPT, unlike N,N-DMT, caused head twitch responses in a mouse model.
The head twitch response was effectively blocked by the selective serotonin 5-HT2A antagonist M100907.
In a rat model, 5-MeO-DIPT showed a 75% generalization from LSD, indicating some similarity in effects.
M100907 abolished the interoceptive effects of 5-MeO-DIPT, while WAY-100635 had no significant impact.
5-MeO-DIPT exhibited micromolar affinity for 5-HT2A and 5-HT2C receptors, and higher affinity for 5-HT1A receptors.

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Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT 1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT 2A and 5-HT 2C receptors, but much higher affinity for 5-HT 1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT 2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT 1A receptor.

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Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats

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