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

Fantegrossi, William E.; Harrington, Andrew W.; Kiessel, Christina Lynn; Eckler, J.R.; Rabin, Richard A.; Winter, J.C.; Coop, Andrew; Rice, Kenner C.; Woods, James H.

doi:10.1016/j.pbb.2005.12.015

Cited by 130 publications

(90 citation statements)

References 32 publications

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“…That head-twitching generated by efavirenz is mediated by the 5-HT 2A receptor is supported by its inability to induce such a response in 5-HT 2A -KO mice. The relatively low affinity of efavirenz for the 5-HT 2A receptor is a likely explanation as to why we needed a relatively high intraperitoneal dose to elicit an effect in vivo and is consistent with receptor affinity and in vivo potency data for other hallucinogens acting via the 5-HT 2A receptors, including some with low affinity and potency such as 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) (Fantegrossi et al, 2006;Fantegrossi et al, 2008). This may also help to explain the reduced duration and intensity of the head-twitch response to efavirenz compared with other hallucinogens (González-Maeso et al, 2007).…”

Section: Discussionsupporting

confidence: 65%

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

Gatch

Kozlenkov

Huang

et al. 2013

Neuropsychopharmacol

109

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Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABA A and 5-HT 2A receptors. In rodents, interaction with the 5-HT 2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT 2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT 2A -knockout, mice. Despite having GABA A -potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that selfadminister cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT 2A receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.

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Section: Discussionsupporting

confidence: 65%

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

Gatch

Kozlenkov

Huang

et al. 2013

Neuropsychopharmacol

109

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“…The cataleptic states observed subsequent to 5-MEO-DIPT administration are also associated with 5-HT 2 agonists. A more recent report has confirmed that 5-MEO-DIPT binds to the 5-HT 2A , 5HT 2C , and 5-HT 1A receptors (the only three receptors investigated in that study) (Fantegrossi et al, 2006). No other data exist describing potential mechanisms of action for 5-MEO-DIPT or the effects it might have on physiology and/or behavior in humans or animals.…”

Section: Introductionmentioning

confidence: 58%

“…While reductions in exploration of a novel environment might be attributed to differences in anxiety, the fact that the 5-MEO-DIPT-treated animals did not spend more time in the periphery would suggest that other factors may have been more important for the reduced locomotor levels. Other drugs that stimulate the 5-HT 2C receptor have been shown to produce hypolocomotion (Gleason et al, 2001) as well and as stated above, there is now evidence that 5-MEO-DIPT has some affinity for the 5-HT 2C receptor (Fantegrossi et al, 2006). One potential confound for the reduced locomotor scores would be if the animals were engaging in stereotypy more than the salinetreated animals, however that was not the case, and in fact the opposite was true during the initial phase of locomotor assessment.…”

Section: Effects Of 5-meo-diptmentioning

confidence: 75%

Alterations in Body Temperature, Corticosterone, and Behavior Following the Administration of 5-Methoxy-Diisopropyltryptamine (‘Foxy’) to Adult Rats: a New Drug of Abuse

Williams

Herring

Schaefer

et al. 2006

Neuropsychopharmacol

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Many drugs are used or abused in social contexts without understanding the ramifications of their use. In this study, we examined the effects of a newly popular drug, 5-methoxy-diisopropyltryptamine (5-MEO-DIPT; 'foxy' or 'foxy-methoxy'). Two experiments were performed. In the first, 5-MEO-DIPT (0, 10, or 20 mg/kg) was administered to rats four times on a single day and animals were examined 3 days later. The animals that received 5-MEO-DIPT demonstrated hypothermia during the period of drug administration and delayed mild hyperthermic rebound for at least 48 h. Corticosterone levels in plasma were elevated in a dose-dependent manner compared to saline-treated animals with minor changes in 5-HT turnover and no changes in monoamine levels. In experiment 2, rats were examined in behavioral tasks following either 0 or 20 mg/kg of 5-MEO-DIPT. The animals treated with 5-MEO-DIPT showed hypoactivity and an attenuated response to ( + )-methamphetamine-induced stimulation (1 mg/kg). In a test of path integration (Cincinnati water maze), 5-MEO-DIPT-treated animals displayed deficits in performance compared to the saline-treated animals. No differences were noted in the ability of the animals to perform in the Morris water maze or on tests of novel object or place recognition. The data demonstrate that 5-MEO-DIPT alters the ability of an animal to perform certain cognitive tasks, while leaving others intact and disrupts the endocrine system. 5-MEO-DIPT may have the potential to induce untoward effects in humans.

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“…Tryptamines share their core structure with the neurotransmitter serotonin (5-hydroxytryptamine ). The psychoactive effects of hallucinogens, including those of tryptamines, are thought to be mediated mainly by the 5-HT 2A receptor (Glennon et al, 1984;Nichols, 2004;Titeler et al, 1988;Vollenweider et al, 1998) but may also be modulated by interactions with other targets, including other 5-HT receptors, monoamine transporters, and trace amineassociated receptors (Baumeister et al, 2014;Bunzow et al, 2001;Cozzi et al, 2009;Fantegrossi et al, 2006;McKenna et al, 1990;Nagai et al, 2007;Nichols, 2004;Ray, 2010). Structural alterations of tryptamines have been shown to result in different pharmacological and psychoactive profiles (Araujo et al, 2015;McKenna et al, 1990;Repke et al, 1985;Shulgin and Shulgin, 1997;Tittarelli et al, 2015;Trachsel et al, 2013).…”

Section: Introductionmentioning

confidence: 99%