ACS Pharmacology & Translational Science
August 18, 2026
Richard A. Glennon, Maƚgorzata Dukat
Abstract Isotryptamines, or 2-(1-indolyl)ethylamines, are positional or geometric isomers of tryptamines where the aminoethyl substituent has been relocated from the indole 3-position to the N1-position. Early studies with these types of agents relied on peripheral tissue assays for examination of their serotonin (5-hydroxytryptamine; 5-HT) receptor affinities to investigate structure–affinity...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 2, 2026
Maya C Gaines-Smith, Justin M Silverman, Michael Fiorillo et al.
3 citations
The psychoactive entactogen 3,4-methylenedioxymethamphetamine (MDMA), widely known as a recreational drug, is gaining renewed attention as a potential psychotherapeutic adjunct for treatment-resistant psychiatric disorders, yet its neurobiological mechanisms - particularly those related to its stereoisomers and sex-specific effects - remain poorly understood. Here, we report stereoselective and...
Psychopharmacology
June 1, 2025
Carmen Abate, Richard Young, Małgorzata Dukat et al.
2 citations
Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical...
ACS Pharmacology & Translational Science
June 14, 2024
Richard A Glennon, Małgorzata Dukat
21 citations
1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, or DOX where X = -I) was first synthesized in 1973 in a structure-activity study to explore the effect of various aryl substituents on the then newly identified, and subsequently controlled, hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, or DOX where X = -CH3). Over time, DOI was found to be a serotonin (5-HT)...
ACS Pharmacology & Translational Science
December 8, 2023
Richard A Glennon, Mal Gorzata Dukat
3 citations
α-Ethyltryptamine (AET) is quite an interesting, but perhaps long-forgotten, centrally acting agent. Known for more than 75 years, AET was once clinically available as an antidepressant but was withdrawn shortly after its introduction. AET was subsequently controlled as a U.S. Schedule I substance due to its perceived abuse liability and/or toxicity but remains an agent of interest....
Australian Journal of Chemistry
July 17, 2023
Richard A Glennon, Małgorzata Dukat
Quipazine, first identified in the 1960s, has been the topic of >1000 published papers. On the basis of available 5-HT2 serotonin receptor radioligand binding data and various preclinical studies, it might be thought that quipazine bears the hallmarks of a classical hallucinogen or psychedelic agent – agents currently being examined for their potential use in treating certain neuropsychiatric...
Frontiers in Pharmacology
2023
Prithvi Hemanth, Pallavi Nistala, Vy T Nguyen et al.
4 citations
Certain 4-substituted analogs of 1-(2,5-dimethoxyphenyl)isopropylamine (2,5-DMA) are psychoactive classical hallucinogens or serotonergic psychedelic agents that function as human 5-HT2A (h5-HT2A) serotonin receptor agonists. Activation of a related receptor population, h5-HT2B receptors, has been demonstrated to result in adverse effects including cardiac valvulopathy. We previously published...
Pharmacology, biochemistry, and behavior
March 2007
Richard A Glennon, Richard Young, Małgorzata Dukat et al.
N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (methylenedioxymethamphetamine, MDMA, Ecstasy) and its structurally abbreviated congener N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA) are chemically related designer drugs, and PMMA is sometimes sold on the clandestine market as a substitute for MDMA. Prior drug discrimination studies have found that MDMA...
Pharmacology, biochemistry, and behavior
October 1, 2006
Richard A Glennon, Tatiana Bondareva, Richard Young
alpha-Ethyltryptamine (etryptamine, alpha-ET) is a drug of abuse that first appeared on the clandestine market in the mid-1980s. Its pharmacological actions are poorly understood. In this investigation, it is reported for the first time that alpha-ET serves as a training drug in drug discrimination studies. Male Sprague-Dawley rats were trained to discriminate (30-min pretreatment time) 2.5...
Pharmacology, biochemistry, and behavior
August 1, 2004
Nantaka Khorana, Manik R Pullagurla, Małgorzata Dukat et al.
21 citations
Two agents gaining popularity on the illicit drug market are the phenylalkylamines 4-MTA and 2C-T-7 [or 1-(4-methylthiophenyl)-2-aminopropane and 2-(2,5-dimethoxy-4-n-propylthiophenyl)-1-aminoethane, respectively]. At this time, there exists a paucity of information on the behavioral actions of these sulfur-containing agents. The present investigation examined these agents, and the N-monomethyl...
Pharmacology, biochemistry, and behavior
July 2003
J R Eckler, J Chang-Fong, R A Rabin et al.
The present investigation was undertaken to test the hypothesis that known metabolites of the phenylethylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) are pharmacologically active. This hypothesis was tested by evaluating the ability of racemic DOM metabolites 2-O-desmethyl DOM (2-DM-DOM) and 5-O-desmethyl DOM (5-DM-DOM) to substitute for the stimulus properties of...
Pharmacology, biochemistry, and behavior
May 2002
Richard A Glennon, Richard Young
1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) is a drug of abuse that is known to produce stimulus effects similar to those of the stimulant phenylalkylamine (+)amphetamine and the hallucinogenic phenylalkylamine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Earlier, a working model was described to account for the stimulus effects produced by phenylalkylamines. Such agents can...
Pharmacology, biochemistry, and behavior
2001
J B Rangisetty, M L Bondarev, J Chang-Fong et al.
14 citations
Psychoactive phenylisopropylamines can produce one or more of several different stimulus effects in animals. These effects are typified by the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the central stimulant amphetamine, and by N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA), an agent whose actions are not yet well understood. The optical isomers of two...
Pharmacology, biochemistry, and behavior
2001
S S Hong, R Young, Richard A Glennon
alpha-Ethyltryptamine (alpha-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, alpha-ET substituted for MDMA. These previous studies employed racemic alpha-ET. Because psychoactive...
Pharmacology, biochemistry, and behavior
1997
Richard A Glennon, R Young, Małgorzata Dukat et al.
48 citations
The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It...
Pharmacology, biochemistry, and behavior
October 1993
R A Glennon
One-carbon homologation of phenylalkylamine or indolylalkylamine hallucinogens containing an alpha-methyl substituent typically results in a reduction of hallucinogenic potency; however, this same structural change has little to no effect on agents that produce MDMA-like effects. In the present investigation, rats trained to discriminate 1.5 mg/kg of MDMA (3,4-methylenedioxymethamphetamine)...
Pharmacology, biochemistry, and behavior
December 1992
R A Glennon, R Higgs, R Young et al.
Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the...
Pharmacology, biochemistry, and behavior
March 1, 1992
N A Darmani, B R Martin, Richard A Glennon
48 citations
The acute and chronic effects of cocaine were evaluated on the 5-hydroxytryptamine (5-HT)-receptor 5-HT2 mediated behavioral function, the head-twitch response (HTR), in mice. In a recent study, we reported that the (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)-induced HTR was dose dependently reduced by cocaine via indirect stimulation of serotonergic 5-HT1A and adrenergic...
Annals of the New York Academy of Sciences
October 1, 1990
Milt Teitler, Sigrun Leonhardt, Nathan M. Appel et al.
33 citations
The data presented herein appear to strongly implicate the brain 5HT2 receptor as the site-of-action of the hallucinogenic PIAs and LSD. If so, this discovery represents a major step in understanding the molecular pharmacology of hallucinogenic drugs. Using radioactive hallucinogenic drugs, detailed properties of brain 5HT2 receptors indicating the interaction of 5HT2 receptors with GTP-binding...
Pharmacology, biochemistry, and behavior
August 1, 1990
N A Darmani, B R Martin, U Pandey et al.
245 citations
To investigate the possible functional relationship between 5-HT1 and 5-HT2 receptors, we studied the effects of a nonselective 5-HT agonist (5-MeO DMT), a 5-HT1A-selective (8-OH-DPAT) and a 5-HT1B/5-HT1C-selective (TFMPP) agonist on the head-twitch behavior induced by the putative 5-HT2-selective receptor agonist (+/-)-DOI. In the mouse (+/-)-DOI produced the head-twitch response in a...
Pharmacology, biochemistry, and behavior
August 1989
R A Glennon, B R Misenheimer
Tests of stimulus generalization were conducted using rats trained to discriminate 1.5 mg/kg of N-monomethyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane HCl (MDMA) from saline in order to determine if two structurally related analogs (MDE and N-OH MDA) would produce similar stimulus effects. The MDMA-stimulus (MDMA, ED50 value = 0.76 mg/kg) generalized both to MDE (ED50 value = 0.73 mg/kg) and...
Psychopharmacology
1989
B Sadzot, J M Baraban, R A Glennon et al.
It has been shown that the hallucinogenic potencies of LSD, the phenylisopropylamines, such as DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) and DOI (4-iodo-2,5-dimethoxyphenylisopropylamine), and the indolealkylamines, such as DMT (dimethyltryptamine) and 5-OMe-DMT (5-methoxy-dimethyltryptamine), strongly correlate with their in vitro 5-HT2 receptor binding affinities in rat cortical...
Pharmacology, biochemistry, and behavior
July 1988
R A Glennon, M Titeler, R A Lyon
4-Bromo-2,5-dimethoxyphenethylamine (alpha-desMe DOB) is a psychoactive agent that may possess significant abuse potential. Because of its structural similarity to the established hallucinogen 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB), and because almost no pharmacological data are available on this agent, we undertook this preliminary investigation. alpha-DesMe DOB (Ki = 1 nM), like...
Pharmacology, biochemistry, and behavior
March 1988
R A Glennon, M Yousif, G Patrick
Using a standard two-lever operant procedure, groups of rats were trained to discriminate intraperitoneal doses of the phenylisopropylamines (+)amphetamine (1.0 mg/kg) or racemic 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM; 1.0 mg/kg) from saline using a VI 15-sec schedule of reinforcement for food reward. Once trained, the animals were administered doses of several methylenedioxy...
Psychopharmacology series
1988
R A Glennon
Various direct- and indirect-acting serotonin (5-HT) agonists serve as training drugs in tests of stimulus control of behavior; such agents include: 5-hydroxytryptophan, 5-methoxy-N,N-dimethyltryptamine, and fenfluramine. However, with the recent discovery of multiple populations of central 5-HT binding sites, the concept of site-selective serotonergic agents needs to be addressed. Certain...