Structure-Activity Relationships of Phenethylamine Hallucinogens

Nichols, David E.

doi:10.1002/jps.2600700802

Cited by 52 publications

(34 citation statements)

References 98 publications

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“…Early studies of Ecstasy users in both Australia and the US created an impression in the ®eld that Ecstasy had generally few negative health effects, (Beck and Rosenbaum, 1994;Moore, 1993;Peroutka et al, 1988;Solowij et al, 1992) and was a relatively benign substance (Downing, 1986;Fromberg, 1990;Nichols and Glennon, 1984). Indeed, Solowij and colleagues reported that only 2% of their sample had ever felt dependent on Ecstasy', although 47% believed that`addiction' to the drug was possible.…”

Section: Introductionmentioning

confidence: 93%

Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria

Cottler

Womack

Compton

et al. 2001

Human Psychopharmacology

150

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As part of an ongoing National Institute on Drug Abuse study on the reliability of DSM substance use disorders, 173 adolescents and young adults have been interviewed to date with the CIDI-Substance Abuse Module (SAM) to determine use and abuse of and dependence on 'club drugs' and other substances. Respondents are recruited from a substance abuse program, high school ads, college dorm flyers, the internet and chain referral. Retest interviews after 5 days determined the reliability of responses. Ecstasy use was reported by 52 respondents (30%); of these users 52% were female and 23% were non-white. Nearly all users (94%) reported recent Ecstasy use. Among Ecstasy users, 'continuing to use despite knowledge of physical or psychological harm' was the most prevalent dependence criterion (63%), with excellent retest agreement (kappa = 0.66). Withdrawal (59%) and tolerance (35%) were also commonly reported dependence criteria. Hazardous use was the most commonly reported abuse symptom. Most surprising were the rates of Ecstasy use disorders: 43% met DSM-IV criteria for dependence; 34% met criteria for abuse; only 23% met neither. This is the first effort to assess the reliability of Ecstasy abuse and dependence, and the first to determine abuse and dependence using criteria specific to Ecstasy. The importance of additional studies and the relevance of such work to DSM-V are discussed. Copyright 2001 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 93%

Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria

Cottler

Womack

Compton

et al. 2001

Human Psychopharmacology

150

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“…To complement the discussion here the reader is encouraged to read an earlier review on this topic, 43 as well as a more recent extensive review on phenethylamine 5-HT 2A agonists. 44 The prototype for this class is mescaline 32, a simple trimethoxy phenethylamine that was first isolated from the peyote cactus, Lophophora williamsii.…”

Section: Phenethylamines and Congenersmentioning

confidence: 99%

Structure–activity relationships of serotonin 5‐HT_2A agonists

Nichols

2012

WIREs Membr Transp Signal

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Of the 14 known types of serotonin receptors one of the most extensively studied is the 5-HT 2A (5-hydroxytryptamine) receptor. In the brain, this receptor plays a key role in regulation of cortical function and cognition, appears to be the principal target for the hallucinogenic/psychedelic drugs such as lysergic acid diethylamide (LSD), and also is a target for the newest atypical antipsychotic agents, which are antagonists or inverse agonists at this site. Among the structure-activity relationships that are known for this receptor type, there are three chemical classes of agonists: tryptamines, ergolines, and phenethylamines. Important structural features are identified for agonist activity and some of these agonists have features in common. In addition to effects at the receptor will be the focus, these drugs are also hallucinogenic (psychedelic) agents, and much of the SAR was developed on the basis of effects in humans, before modern pharmacological techniques were available. A certain amount of our knowledge therefore relies on those human studies.

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“…A direct comparison of several of these compounds and their stereoisomers in the same group of animals, under the same self-administration contingencies, might reveal important structure-activity relationships (see, e.g., Anderson et al 1978;Nichols 1981) for the reinforcing effects of MDMA-like drugs. Such a study has not yet been conducted, but we have studied a small sample of these compounds in rhesus monkey self-administration paradigms, and a review of these data may be illustrative.…”

Section: Reinforcing Effects Of Mdma and Its Analogsmentioning

confidence: 99%

Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

Fantegrossi

2006

Psychopharmacology

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Rationale: Many animal models relevant to the persistent effects of drugs of abuse necessitate the application of interspecies dose scaling procedures to approximate drug administration regimens in humans, but drug self-administration procedures differ in that they allow animal subjects to control their own drug intake. Objectives: This report reviews the reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA), its enantiomers, and several structural analogs in rhesus monkeys, paying particular attention to the pharmacological mechanisms of such reinforcing effects, the development of structure activity relationships among these compounds, the stability of MDMA self-administration behavior over time, and the persistent effects of selfadministered MDMA on monoamines. Results: The methylenedioxy amphetamine congeners MDMA, 3, 4-methylenedioxyamphetamine, N-ethyl-3,4-methylenedioxyamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine function as reinforcers in rhesus monkeys, maintaining self-administration behavior greater than that engendered by contingent saline but less than that engendered by traditional psychostimulants. These findings are remarkable as structurally distinct serotonergic hallucinogen-like drugs do not maintain reliable selfadministration in laboratory animals. During prolonged MDMA self-administration, MDMA-maintained responding progressively weakens, and MDMA eventually fails to maintain significant self-administration. The neurochemical correlates of this effect have not yet been identified. Conclusions: Procedures in which MDMA and related compounds are self-administered can be established in rhesus monkeys. These techniques can be used to engender contingent MDMA exposure without resorting to controversial methods of interspecies dose scaling. As such, further application of self-administration methods may provide important new insights into the persistent effects of MDMA on brain and behavior in nonhuman primates.

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Structure-Activity Relationships of Phenethylamine Hallucinogens

Cited by 52 publications

References 98 publications

Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria

Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria

Structure–activity relationships of serotonin 5‐HT_2A agonists

Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

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Structure-Activity Relationships of Phenethylamine Hallucinogens

Cited by 52 publications

References 98 publications

Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria

Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM‐IV criteria

Structure–activity relationships of serotonin 5‐HT2A agonists

Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

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Structure–activity relationships of serotonin 5‐HT_2A agonists