Structure-Activity Relationships of MDMA-Like Substances

Nichols, David E.; Oberlender, Robert

doi:10.1037/e496472006-001

Cited by 24 publications

(19 citation statements)

References 39 publications

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“…One difference is that rather than the stimulus effects of MDMA being enhanced by a hallucinogenic agent (Schechter, 1998a), the present investigation demonstrates that the stimulus effects of a hallucinogenic agent (i.e., DOM) were enhanced by MDMA. Furthermore, the Schechter study employed a strain of rat (Fawn-Hooded) different from that used here (Sprague-Dawley), and it has been demonstrated that MDMA-stimulus generalization occurs to LSD in serotonergically-dysfunctional Fawn-Hooded rats (Schechter, 1998b) but not in Sprague-Dawley rats (Nichols and Oberlender, 1989). Also, LSD is a potent, but non-selective serotonin receptor ligand with 5-HT 1A agonist action of its own (i.e., inhibition of cAMP accumulation) whereas, in contrast, DOM lacks significant 5-HT 1A receptor affinity and agonist action (Pauwels et al, 1993).…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have demonstrated that MDMA stimulus generalization occurs to (±)8-OH DPAT, and that (±)8-OH DPAT enhances the stimulus actions of DOM (Glennon, 1991; Glennon and Young, 2000). However, DOM and MDMA failed to substitute for one another in tests of stimulus generalization regardless of which was employed as training drug (Glennon et al, 1982, 1986; Glennon, 1989; Nichols and Oberlender, 1989). As shown in Figure 1, MDMA failed to substitute for a DOM stimulus.…”

Section: Discussionmentioning

confidence: 99%

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Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats

Khorana

Young

Glennon

2009

Pharmacology Biochemistry and Behavior

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Co-administration of the 5-HT1A serotonin receptor agonist (±)8-hydroxy-2-(N,N-di-n-propylamino) tetralin [(±)8-OH DPAT] enhances the discriminative stimulus effects of the classical hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats. In the present investigation, using Sprague-Dawley rats trained to discriminate DOM (1.0 mg/kg) from saline vehicle under a VI-15s schedule of reinforcement, it was shown that the stimulus-enhancing actions of 8-OH DPAT are related more to its R(+)-isomer than to its S(−)-enantiomer, and that the (±)- and R(+)8-OH DPAT-induced effects are antagonized by the 5-HT1A receptor antagonist NAN-190. (±)8-OH DPAT and its isomers substitute in rats trained to discriminate the designer drug N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; methylenedioxymethamphetamine) from vehicle indicating some similarity of effect. On this basis, it was hypothesized that MDMA might be capable of enhancing the DOM stimulus. Co-administration of MDMA with low (i.e., 0.1 and 0.3 mg/kg) doses of DOM resulted in greater DOM-appropriate responding than engendered by administration of DOM alone. As such, the present findings are the first to demonstrate an MDMA-induced enhancing effect on the discriminative stimulus actions of a classical hallucinogen. The results also suggest that a 5-HT1A serotonin receptor mechanism might contribute to this phenomenon.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats

Khorana

Young

Glennon

2009

Pharmacology Biochemistry and Behavior

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“…However, MDMA does not substitute for the potent hallucinogen, DOM, in animals trained to discriminate DOM from saline (Glennon et al, 1982;Nichols et al, 1986). Thus, MDMA appears to have significant stimulant activity but little or no hallucinogenic activity (Gletmon, Yousif & Patrick, 1988;Nichols & Oberlender, 1989), at least at the doses tested. Since the MDMA cue can be partially blocked by the dopamine receptor antagotiist haloperidol (Schecter, 1989), it would seem that some of MDMA's discriminative stimulus effects are mediated by dopamine.…”

Section: Behavioral Effectsmentioning

confidence: 99%

3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans

1994

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(+/-)3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"), a ring-substituted amphetamine derivative first synthesized in 1914, has emerged as a popular recreational drug of abuse over the last decade. Pharmacological studies indicate that MDMA produces a mixture of central stimulant and psychedelic effects, many of which appear to be mediated by brain monoamines, particularly serotonin and dopamine. In addition to its pharmacologic actions, MDMA has been found to possess toxic activity toward brain serotonin neurones. Serotonergic neurotoxicity after MDMA has been demonstrated in a variety of experimental animals (including non-human primates). In monkeys, the neurotoxic dose of MDMA closely approaches that used by humans. While the possibility that MDMA is also neurotoxic in humans is under investigation, other adverse effects of MDMA in humans have been documented, including various systemic complications and a number of untoward neuropsychiatric sequelae. Notably, many of the adverse neuropsychiatric consequences noted after MDMA involve behavioral domains putatively influenced by brain serotonin (e.g., mood, cognition and anxiety). Given the restricted status of MDMA use, retrospective clinical observations from suspecting clinicians will probably continue to be a primary source of information regarding MDMA's effects in humans. As such, this article is intended to familiarize the reader with the behavioral pharmacology and toxicology of MDMA, with the hope that improved recognition of MDMA-related syndromes will provide insight into the function of serotonin in the human brain, in health as well as disease.

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“…Like methamphetamine, MDMA is a potent releaser of catecholamine neurotransmitters (i.e., epinephrine, norepinephrine, and dopamine) via action at presynaptic reuptake sites. MDMA is also a potent releaser of pre-synaptic serotonin (De la Torre et al, 2004; Nichols & Oberlender 1989; 1990; Nichols, 1994). Like mescaline and other classic hallucinogens, the subjective effects of MDMA are also attenuated by the 5-HT2AR antagonist ketanserin (Liechti et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Clinical applications of hallucinogens: A review.

Garcia-Romeu

Kersgaard

Addy³

2016

Experimental and Clinical Psychopharmacology

157

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Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value.

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Structure-Activity Relationships of MDMA-Like Substances

Cited by 24 publications

References 39 publications

Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats

Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats

3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans

Clinical applications of hallucinogens: A review.

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