Behavioural pharmacology
December 1, 2005
William E Fantegrossi, Kelly M Kugle, Leander J Valdes et al.
80 citations
Salvinorin A, a natural compound from the Mexican mint Salvia divinorum, is the first known naturally occurring kappa-opioid receptor agonist with a novel chemical structure distinct from other opioids. In mice, salvinorin A caused rapid but short-lived sedation and motor incoordination, similar to the effects of the mu-agonist remifentanil and the synthetic kappa-agonist U69,593. Using selective antagonists, the motor effects of salvinorin A and U69,593 were shown to be mediated by kappa-opioid receptors, while remifentanil's effects involved mu-receptors. Salvinorin A and U69,593 differed in their susceptibility to antagonism by nor-binaltorphamine, suggesting salvinorin A may bind to the kappa-receptor differently than traditional kappa-agonists. This raises the possibility that developing other diterpene-based opioids could yield therapeutic compounds.
Psychopharmacology
September 1, 2005
William E Fantegrossi, Andrew W Harrington, Justin R Eckler et al.
72 citations
The hallucinogen 2C-T-7 produces head twitch responses in mice and serves as a discriminative stimulus in rats, effects that are blocked by a selective 5-HT2A antagonist. In drug discrimination tests, 2C-T-7 partially generalized (75%) to the LSD cue in rats and acted as a discriminative stimulus itself, with those interoceptive effects also attenuated by the 5-HT2A antagonist. Binding studies show 2C-T-7 has nanomolar affinity for 5-HT2A and 5-HT2C receptors and lower affinity for 5-HT1A receptors. The antagonism of its behavioral effects strongly suggests the 5-HT2A receptor is an important site of action for this compound.
The Journal of pharmacology and experimental therapeutics
December 1, 2014
Douglas A Smith, Jessica M Bailey, Diarria Williams et al.
31 citations
Tolerance developed to the head twitch response (HTR) elicited by daily administration of the phenethylamine-derived hallucinogens DOI and 2C-T-7 in mice, but not to the tryptamine-derived drugs DPT and DIPT. Tolerance to DOI was insurmountable by increasing dose, and cross-tolerance to 2C-T-7 and DPT was also insurmountable in DOI-tolerant mice. These results suggest that phenethylamine-derived 5-HT2A agonists may be limited for chronic therapeutic use by rapid tolerance development that persists even when switching to a different structural class. Tryptamine-derived hallucinogens may have a reduced tolerance potential and could be more suitable for long-term administration.
Psychedelic medicine (New Rochelle, N.Y.)
September 1, 2023
Harpreet Kaur, Sedat Karabulut, James W Gauld et al.
10 citations
Autism spectrum disorder (ASD) involves social communication deficits and repetitive behaviors, with no approved drugs for its core symptoms. Existing medications like aripiprazole and risperidone treat irritability but can cause side effects such as weight gain and sedation. Drugs with pro-social effects, including MDMA and its analogue MBDB, may help address social anxiety and avoidance in ASD. This review examines the pharmacology of methylenedioxy amphetamine analogues (MDXX drugs), focusing on their binding sites, metabolism, and structure-activity relationships. It emphasizes how individual stereoisomers and their racemic mixtures shape drug effects. The authors propose that MDXX compounds offer a promising chemical space for developing safer, more effective treatments for ASD.
Journal of psychopharmacology (Oxford, England)
January 1, 2026
Jack E Henningfield, Sandra D Comer, Matthew L Banks et al.
5 citations
A panel of abuse potential experts convened to discuss challenges in assessing the abuse potential of novel drugs, especially psychedelics and cannabinoids. The U.S. Controlled Substances Act scheduling process, intended to balance public safety with medicinal access, can be overly restrictive when abuse potential is overestimated, as postmarketing evaluations have suggested for some substances. Existing methods recommended by the FDA are generally reliable for many drug categories but require modifications—such as behavioral economic assessments and broader outcome measures in human abuse potential studies—to accurately characterize newer agents. The commentary emphasizes the need for updated approaches to ensure valid scheduling decisions that protect public health without hindering access to beneficial medicines.
The FASEB Journal
March 1, 2008
Kevin Sean Murnane, Leonard L Howell, William E Fantegrossi
MDMA has both stimulant and hallucinogen-like effects, and its two isomers, R(−)-MDMA and S(+)-MDMA, produce different behavioral effects: R(−)-MDMA is hallucinogen-like, while S(+)-MDMA is stimulant-like. In this study, mice were trained to discriminate each isomer from a vehicle in a two-lever operant task. Drugs with hallucinogen-like effects (2C-T-7, DPT) and stimulant-like effects (amphetamine, cocaine) were substituted for the training isomer. Results showed efficacy differences within chemical classes and potency differences within behavioral classes, clarifying the complex discriminative stimulus properties of MDMA isomers.