Psychopharmacology
March 1, 2014
Amy J Eshleman, Michael J Forster, Katherine M Wolfrum et al.
72 citations
Six substituted phenethylamines (2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC) depress mouse locomotor activity, though 2C-D and 2C-E stimulate activity at low doses. Most fully substitute for hallucinogenic training compounds in rats, but none fully substitute for methamphetamine. All are full agonists at 5-HT2A and 5-HT2C receptors in inositol phosphate assays, and most are partial to full agonists in 5-HT2A arachidonic acid release assays, except 2C-I (antagonist). Only 2C-I shows moderate affinity for the serotonin transporter. The discriminative stimulus effects of most compounds resemble hallucinogens, not methamphetamine, but 2C-T-2 does not produce hallucinogen-like effects despite being a full agonist at 5-HT2A and 5-HT2C receptors.
Journal of Pharmacology and Experimental Therapeutics
April 8, 2011
Michael B. Gatch, Michael J. Forster, Aaron Janowsky et al.
42 citations
Three synthetic hallucinogens—DIPT, 5-MeO-DET, and 5-MeO-AMT—produced behavioral effects in rats similar to those of known abused hallucinogens like LSD and DMT, but not to psychostimulants like cocaine or methamphetamine. DIPT fully substituted for DMT and DOM, while 5-MeO-DET fully substituted for DMT; none fully substituted for cocaine or methamphetamine. All three compounds acted at serotonin 5-HT(1A) and 5-HT(2A) receptors and blocked serotonin reuptake. 5-MeO-AMT also weakly released serotonin and blocked dopamine uptake. DIPT and 5-MeO-DET may have abuse liability similar to hallucinogens and were hazardous at high doses, causing activity and lethality.
PloS one
January 1, 2013
Tamara Antonio, Steven R Childers, Richard B Rothman et al.
36 citations
Iboga alkaloids, including ibogaine, its metabolite noribogaine, and the synthetic compound 18-methoxycoronaridine (18-MC), were tested for their ability to activate the μ-opioid receptor (MOR), a common target of opioid drugs. In rat thalamic membranes, all three compounds acted as antagonists, blocking the receptor rather than activating it, with functional Ke values ranging from 3 μM for ibogaine to 13 μM for noribogaine and 18-MC. None of the compounds stimulated MOR-related G protein activity in cells expressing human or rat MORs, and only limited partial agonist effects were seen in mouse MOR-expressing cells. The findings indicate that an opioid agonist mechanism does not explain these alkaloids' effects on opioid withdrawal, supporting a novel mechanism of action and justifying further search for alternative targets.