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John S. Partilla

16 papers in the library · 1,569 citations · publishing 2000-2026

Papers

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Serotonin Transporter Blockade Reduces the Psychedelic-Like Effects of 4-Methoxy- N -methyl- N -isopropyltryptamine and Related Analogs

ACS Chemical Neuroscience May 27, 2026 Grant C. Glatfelter, Serena S. Schalk, Donna Walther et al.

High Resolution Image Download MS PowerPoint Slide Tryptamine psychedelics induce psychoactive effects via agonist actions at serotonin 2A receptors (5-HT 2A ), but the compounds are generally nonselective. 4-Methoxy- N -methyl- N -isopropyltryptamine (4-MeO-MiPT) is a 5-HT 2A agonist which also blocks the 5-HT transporter (SERT) and has blunted visual and other psychedelic effects in humans....

Serotonergic Polypharmacology of 2-Halogenated Tryptamines.

bioRxiv : the preprint server for biology April 21, 2026 Jeanine Yacoub, Elena Bray, Jude Bayyat et al.

Serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) show therapeutic promise for psychiatric and neurodegenerative disorders but may be limited by liabilities from serotonin (5-HT)-2A mediated psychoactive effects and potential cardiotoxicity via 5-HT2B activation. To address these limitations, we designed and synthesized...

Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice.

Psychopharmacology May 17, 2025 Shelby A. McGriff, Jacquelin C Hecker, Alexander D. Maitland et al. 12 citations

The head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lysergamides, tryptamines). To examine potential sex...

Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy-N,N-dimethyltryptamine Analogs in Mice.

ACS Chemical Neuroscience December 18, 2024 Grant C. Glatfelter, Allison A Clark, Natalie G. Cavalco et al. 14 citations

5-methoxy-N,N-dimethyltrytpamine (5-MeO-DMT) analogs are used as recreational drugs, but they are also being developed as potential medicines, warranting further investigation into their pharmacology. Here, we investigated the neuropharmacology of 5-MeO-DMT and several of its N-alkyl, N-allyl, and 2-methyl analogs, with three major aims: 1) to determine in vitro receptor profiles for the...

Comparative Pharmacological Effects of Lisuride and Lysergic Acid Diethylamide Revisited.

ACS Pharmacology & Translational Science March 8, 2024 Grant C. Glatfelter, Eline Pottie, John S. Partilla et al. 28 citations

Lisuride is a non-psychedelic serotonin (5-HT) 2A receptor (5-HT2A) agonist and analogue of the psychedelic lysergic acid diethylamide (LSD). Lisuride also acts as an agonist at the serotonin 1A receptor (5-HT1A), a property known to counter psychedelic effects. Here, we tested whether lisuride lacks psychedelic activity due to a dual mechanism: (1) partial agonism at 5-HT2A and (2) potent...

Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice

ACS Pharmacology & Translational Science November 2, 2022 Eline Pottie, Marilyn Naeem, Vamshikrishna Reddy Sammeta et al. 91 citations

4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing...

Comparative neuropharmacology of N-(2-methoxybenzyl)-2,5-dimethoxyphenethylamine (NBOMe) hallucinogens and their 2C counterparts in male rats.

Neuropharmacology November 1, 2018 Joshua S. Elmore, Ann M Decker, Agnieszka Sulima et al. 59 citations

2,5-Dimethoxyphenethylamines (2C compounds) are 5-HT2A/2C receptor agonists that induce hallucinogenic effects. N-methoxybenzylation of 2C compounds markedly increases their affinity for 5-HT2A receptors, and two such analogs, 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) and 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe),...

Fluorinated phenmetrazine “legal highs” act as substrates for high-affinity monoamine transporters of the SLC6 family

Neuropharmacology October 12, 2017 Felix P. Mayer, Nadine V. Burchardt, Ann M Decker et al. 30 citations

A variety of new psychoactive substances (NPS) are appearing in recreational drug markets worldwide. NPS are compounds that target various receptors and transporters in the central nervous system to achieve their psychoactive effects. Chemical modifications of existing drugs can generate NPS that are not controlled by current legislation, thereby providing legal alternatives to controlled...

Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N‐methoxy positional isomer, N‐methoxymephedrone

Drug Testing and Analysis August 15, 2016 Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh et al. 23 citations

3‐Methoxy‐2‐(methylamino)‐1‐(4‐methylphenyl)propan‐1‐one (mexedrone) appeared in 2015 and was advertised by UK Internet retailers as a non‐controlled mephedrone derivative (2‐(methylamino)‐1‐(4‐methylphenyl)propan‐1‐one), which was of particular interest to countries who operate generic drugs legislation. This study describes the synthesis and analytical characterization of mexedrone and the...

Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3′,4′‐methylenedioxy‐4‐methylaminorex (MDMAR)

Drug Testing and Analysis October 20, 2014 Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh et al. 18 citations

The recent occurrence of deaths associated with the psychostimulant cis-4,4'-dimethylaminorex (4,4'-DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4-methylenedioxy-4-methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis- and trans-MDMAR followed by extensive...

Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes.

Psychopharmacology October 1, 2014 Bruce E. Blough, Antonio Landavazo, Ann M Decker et al. 99 citations

Synthetic hallucinogenic tryptamines, especially those originally described by Alexander Shulgin, continue to be abused in the USA. The range of subjective experiences produced by different tryptamines suggests that multiple neurochemical mechanisms are involved in their actions, in addition to the established role of agonist activity at serotonin 2A (5-HT₂A) receptors. This study evaluated the...

Stereochemistry of mephedrone neuropharmacology: enantiomer‐specific behavioural and neurochemical effects in rats

British Journal of Pharmacology September 26, 2014 Ryan A. Gregg, Michael H. Baumann, John S. Partilla et al. 79 citations

BACKGROUND AND PURPOSE: Synthetic cathinones, commonly referred to as 'bath salts', are a group of amphetamine-like drugs gaining popularity worldwide. 4-Methylmethcathinone (mephedrone, MEPH) is the most commonly abused synthetic cathinone in the UK, and exerts its effects by acting as a substrate-type releaser at monoamine transporters. Similar to other cathinone-related compounds, MEPH has a...

Characterization of a novel and potentially lethal designer drug (±)‐cis‐para‐methyl‐4‐methylaminorex (4,4'‐DMAR, or ‘Serotoni’)

Drug Testing and Analysis May 19, 2014 Simon D. Brandt, Michael H. Baumann, John S. Partilla et al. 37 citations

During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4'-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analog. Analytical characterization of two independent samples obtained from online...

Salvinorin A: allosteric interactions at the mu-opioid receptor.

The Journal of pharmacology and experimental therapeutics February 1, 2007 Richard B Rothman, Daniel L Murphy, Heng Xu et al. 75 citations

Salvinorin A [(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2h-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester] is a hallucinogenic kappa-opioid receptor agonist that lacks the usual basic nitrogen atom present in other known opioid ligands. Our first published studies indicated that Salvinorin A weakly inhibited mu-receptor binding, and...

Effects of “Legal X” Piperazine Analogs on Dopamine and Serotonin Release in Rat Brain

Annals of the New York Academy of Sciences October 1, 2004 Michael H. Baumann, Robert D. Clark, Allison G. Budzynski et al. 71 citations

3,4-Methylenedioxymethamphetamine (MDMA) is a popular illicit drug that evokes transporter-mediated release of serotonin (5-HT) and dopamine (DA) from nerve cells. Recently, drug users have ingested combinations of the piperazine analogs, 1-benzylpiperazine (BZP) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP), in an attempt to mimic the subjective effects of MDMA. In the present study, we...

Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin

Synapse 2000 Richard B Rothman, Michael H. Baumann, Christina M Dersch et al. 933 citations

A large body of evidence supports the hypothesis that mesolimbic dopamine (DA) mediates, in animal models, the reinforcing effects of central nervous system stimulants such as cocaine and amphetamine. The role DA plays in mediating amphetamine-type subjective effects of stimulants in humans remains to be established. Both amphetamine and cocaine increase norepinephrine (NE) via stimulation of...