Journal of Psychoactive Drugs
October 1, 1986
Alexander T. Shulgin
234 citations
MDMA (3,4-methylenedioxymethamphetamine) is a synthetic compound first developed in 1912 by the German pharmaceutical company Merck. Its chemical structure combines features of methamphetamine and mescaline, placing it within the phenethylamine class. The paper traces the historical background of MDMA, describing its initial synthesis, its later emergence as a recreational drug known as ecstasy, and its chemical properties. It explains the molecule's structure, its relationship to other amphetamine derivatives, and how its chemical composition influences its psychoactive effects. The work provides a foundational overview of MDMA's chemistry and historical context, serving as an introduction to the substance for a conference on its pharmacological and psychological implications.
Journal of Medicinal Chemistry
October 1, 1986
David E. Nichols, Andrew J. Hoffman, Robert Oberlender et al.
189 citations
A new phenethylamine derivative, 1-(1,3-benzodioxol-5-yl)-2-butanamine, was synthesized in both racemic and enantiomerically pure forms, along with the related compound MDA. In rats trained to discriminate LSD from saline, only the racemate and R-(-) enantiomer of the alpha-methyl homologue, and the S-(+) enantiomer of the alpha-ethyl primary amine, produced stimulus generalization; other enantiomers and N-methyl derivatives did not. Human studies indicated the N-methyl derivative was nonhallucinogenic but had a novel psychoactive effect. The authors propose this compound as the prototype of a new pharmacological class, termed entactogens, potentially useful in facilitating psychotherapy.
J Neural Transm (Vienna)
September 12, 2009
Nicholas V. Cozzi, Anupama Gopalakrishnan, Lyndsey L. Anderson et al.
144 citations
N,N-dimethyltryptamine (DMT) and related tryptamines inhibit serotonin transport at the serotonin transporter (SERT) and vesicle monoamine transporter (VMAT2) with varying potencies. DMT, MIPT, DPT, and DIPT inhibited serotonin uptake at SERT with Ki values of 4.00, 8.88, 0.594, and 2.32 µM, respectively. At VMAT2, inhibition was weaker, with Ki values of 93, 20, 19, and 19 µM. The tryptamines were poor inhibitors of radioligand binding to these transporters, yielding high binding-to-uptake ratios. This pattern suggests the tryptamines act as transporter substrates rather than uptake blockers, indicating separate substrate and inhibitor binding sites. The transporters may concentrate tryptamines inside neurons for sigma-1 receptor activation and potential release as transmitters.
Journal of Medicinal Chemistry
December 1, 1975
Alexander T. Shulgin, Donald C. Dyer
37 citations
A series of chemically related compounds, 4-alkyl-2,5-dimethoxyphenylisopropylamines with alkyl groups ranging from hydrogen to five-carbon straight chains and a branched four-carbon chain, was synthesized and tested for their ability to mimic serotonin in a sheep umbilical tissue preparation. Among the straight-chain variants, the compound with a three-carbon alkyl group was the most potent, matching its known mind-altering effects in humans.
Ecstasy: The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA
January 1, 1990
Alexander T. Shulgin
35 citations
A complete history of a highly controversial topic is impossible because proponents and skeptics state their beliefs with equal confidence. While some historical facts remain uncontested, many are shaped by opinions that influence interpretation. Other facts are kept secret for legal or privacy reasons, and some are simply lost forever.
Pharmacology
January 1, 1973
Alexander T. Shulgin, T. Sargent, Carolina Lopez Naranjo
33 citations
The compound 3-methoxy-4,5-methylenedioxyphenyl isopropylamine (MMDA) was synthesized and tested for psychodysleptic effects. In animals, its pharmacology was generally unremarkable except for a hypotensive effect in dogs, and the therapeutic index (LD50 rat/MED50 human) was 85. In humans, MMDA enhanced feeling and eyes-closed visual imagery without causing hallucinations or disturbing the sensorium. Reality testing and environmental contact remained intact, though a tendency to withdraw into drowsiness or fantasy occurred. The state of increased emotional availability was easily manipulated in psychotherapy and appeared to enhance insight into subconscious content.
Journal of Pharmaceutical Sciences
July 1, 1979
Richard A. Glennon, Lemont B. Kier, Alexander T. Shulgin
29 citations
The hallucinogenic potency of ten mescaline analogs was analyzed using molecular connectivity. A two-term equation based on structural variation explained 94% of the variance in activity. Substitutions at the 2,5-dimethoxy positions and the nature of the 4-position substituent were important determinants of potency. The equation also made reasonable potency predictions for six additional compounds not included in the original analysis.
Journal of Medicinal Chemistry
February 24, 1998
Matthew Parker, Danuta Marona‐lewicka, Deborah M. Kurrasch et al.
25 citations
Adding a methyl group to the 2 or 5 position of the ring of MDA produces compounds that are more potent and more selective than MDA itself at releasing serotonin in rat brain tissue. The 2-methyl and 5-methyl derivatives were tested in rats trained to distinguish serotonin-releasing drugs from saline, confirming their activity in living animals. These compounds are among the most potent serotonin-releasing agents known and may serve as leads for developing antidepressants that work by releasing serotonin rather than blocking its reuptake.
Journal of Medicinal Chemistry
November 1, 1981
Peyton Jacob, Alexander T. Shulgin
20 citations
Two sulfur-containing analogues of mescaline, 3-thiomescaline and 4-thiomescaline, were synthesized and found to be psychotomimetic in humans, with 4-thiomescaline being 12 times more potent and 3-thiomescaline 6 times more potent than mescaline itself. Three additional analogues of isomescaline were also synthesized but were not psychotomimetic. All five compounds were broken down by bovine plasma monoamine oxidase in the lab, but the rate of this enzymatic degradation did not correlate with their potency as hallucinogens in people.
Journal of Psychedelic Drugs
January 1, 1979
Alexander T. Shulgin
20 citations
This paper reviews the chemistry of phenethylamines structurally related to mescaline, a naturally occurring psychedelic alkaloid. It describes the chemical synthesis, structural variations, and analytical methods such as chromatography used to identify and characterize these compounds. The review covers how modifications to the phenethylamine backbone affect pharmacological activity and discusses the relationship between chemical structure and psychedelic potency. The authors provide a systematic overview of known synthetic routes and analytical techniques relevant to studying mescaline analogs.
Journal of Medicinal Chemistry
May 1, 1983
Peyton Jacob, Alexander T. Shulgin
18 citations
Two thio analogues of the psychotomimetic drugs DOM and DOET were synthesized and tested in humans. The 5-thio isomers are more potent than the 2-thio isomers but are about ten times less potent than the original sulfur-free drugs. The dithio analogue of DOM showed no central activity at a dose roughly 50 times the effective dose of DOM.
Journal of Medicinal Chemistry
July 1, 1984
Peyton Jacob, Alexander T. Shulgin
14 citations
All possible monothio analogues of mono-, di-, and triethoxy homologues of mescaline were synthesized and tested in humans. Modifications at the ring position para to the ethylamine chain, using a sulfur atom, a longer alkyl chain, or both, produce compounds with high central nervous system activity. The 4-n-propoxy and 4-n-butoxy homologues and their corresponding 4-thio analogues were also made and tested. Propyl homologues retain high potency, but a butyl group, with or without sulfur, reduces activity. Meta-ethyl or meta-thio analogues retain some central action, while diethoxy and especially triethoxy homologues are relatively inactive as psychotomimetic drugs.
Journal of Medicinal Chemistry
February 1, 1980
Robert T. Standridge, Henry G. Howell, Hugh A. Tilson et al.
13 citations
A series of new chemical compounds similar to a known hallucinogen were synthesized and tested in animals. Most of the analogues showed low hallucinogenic potential. The compounds were compared with a reference substance in a behavioral model that distinguishes hallucinogenic from non-hallucinogenic drugs. The chemical structures and their effects are discussed.
Journal of Psychoactive Drugs
June 1, 2008
Jan G. Bruhn, Hesham R. Ei-Seedi, Nikolai Stephanson et al.
11 citations
Three new minor alkaloids—lophophine, homopiperonylamine, and lobivine—have been identified in peyote (Lophophora williamsii) and San Pedro (Trichocereus pachanoi) cacti. These are the first psychoactive phenethylamines other than mescaline reported in these species. The discovery suggests that substances resembling Ecstasy may occur naturally, and further investigation of biosynthetic analogues could clarify structure-activity relationships of mescaline. The findings raise the question of whether such natural compounds can be considered designer drugs.
Journal of Labelled Compounds and Radiopharmaceuticals
January 1, 1978
Gisela Braun, Alexander T. Shulgin, Thornton Sargent
9 citations
Imagine tracking a mind-altering substance in the body with precision. Researchers devised a rapid, efficient method to produce a radioactive version of a psychotomimetic agent. By temporarily protecting a key part of the compound, they successfully attached Iodine-123 directly. This innovative process swiftly yielded the desired tagged chemical, ready for use in under 13 hours. This advancement offers a valuable tool for understanding complex brain chemistry.