PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA

Rangisetty, Jagadeesh B.; Bondarev, Mikhail L.; Chang-Fong, Jean; Young, Richard; Glennon, Richard A.

doi:10.1016/s0091-3057(01)00530-5

Cited by 14 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because MDMA possesses both amphetaminergic and PMMA-like character (i.e., stimulus generalization occurs between MDMA and PMMA regardless of which is used as training drug, but only MDMA and not PMMA substitute for the amphetamine in (+)amphetamine trained animals) (Glennon et al, 1997;Rangisetty et al, 2001), it was of interest to determine whether or not either isomer of a-ET would substitute for PMMA. That is, although ( À )a-ET substituted for MDMA, this might be the result of its amphetaminergic actions.…”

Section: Discussionmentioning

confidence: 99%

“…Phenylalkylamines with abuse potential can produce one or more of at least three distinct stimulus effects in animals: a DOM-like or ''hallucinogenic'' effect, an amphetamine-like effect, and a third type of effect for which PMMA, or Nmethyl-(4-methoxyphenyl)-2-aminopropane, has become an example (Glennon, 1999;Glennon et al, 1997;Rangisetty et al, 2001). Evidence suggests that the stimulus effects of DOM involve a 5-HT 2A agonist mechanism whereas the effects of (+)amphetamine seem primarily mediated via a catecholaminergic mechanism (Glennon, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…At this time, the mechanism of action of PMMA as a discriminative stimulus is unknown. Some agents are capable of producing more than one type of effect; for example, MDMA substitutes both for (+)amphetamine and for PMMA (Glennon, 1999;Rangisetty et al, 2001). Furthermore, the stimulus effects of phenylalkylamines can be stereoselective or stereospecific depending upon the agent being examined; that is, both optical isomers or perhaps only a single isomer will substitute.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Discriminative stimulus properties of α-ethyltryptamine optical isomers

Hong

Young

Glennon

2001

Pharmacology Biochemistry and Behavior

Self Cite

View full text Add to dashboard Cite

a-Ethyltryptamine (a-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, a-ET substituted for MDMA. These previous studies employed racemic a-ET. Because psychoactive phenylalkylamines with abuse potential can produce one or more of three distinct stimulus effects (i.e., amphetamine-, DOM-and/or PMMA-like effects) in animals trained to discriminate either the stimulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) from vehicle, and because these effects can be stereoselective, the individual optical isomers of a-ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. ( À )a-ET (ED 50 = 7.8 mg/kg), but not (+)a-ET (maximum of 53% drugappropriate responding), substituted for (+)amphetamine, whereas (+)a-ET (ED 50 = 2.7 mg/kg), but not ( À )a-ET (maximum of 33% drugappropriate responding), substituted for DOM. Both optical isomers of a-ET substituted for PMMA and MDMA with ED 50 values of 1.6 and 1.4 mg/kg (PMMA-trained animals) and 1.3 and 2.0 mg/kg (MDMA-trained animals) for ( À )a-ET and (+)a-ET, respectively. The results of this investigation suggest that both optical isomers of a-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of a-ET resides primarily with its ( À )isomer whereas hallucinogenic or DOM-like character resides primarily with the (+)enantiomer. D

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Discriminative stimulus properties of α-ethyltryptamine optical isomers

Hong

Young

Glennon

2001

Pharmacology Biochemistry and Behavior

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, PMMA shares considerable pharmacological similarities with MDMA, but it lacks the amphetaminergic stimulant component of MDMA. Its stimulant effects were described to be similar to MBDB and dimethoxyamphetamine [44][45][46][47][48]. The only data available on the effects in humans have been published by Shulgin, who described its effects as somewhat different from those of MDMA [49].…”

Section: R S-para-methoxymethamphetamine (Pmma)mentioning

confidence: 99%

Metabolism of Designer Drugs of Abuse

Staack

Maurer

2005

CDM

107

View full text Add to dashboard Cite

Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

show abstract

“…Additionally, a comparative study of the behavioral properties of the optical isomers of PMMA, MBDB, MDA and MDMA indicated that (±)-PMMA generalized to ( S )(+)-MBDB, ( R )(-)-MBDB, ( S )(+)-3,4-DMA, ( R )(-)-3,4 DMA, ( S )(+)-MDMA and (±)-MDMA in rats. In addition, it was suggested also that MBDB and 3,4-DMA are probably closer to PMMA [130]. Interestingly ( R )(-)-PMA, like MDMA, seems also to share an entactogenic-like profile [101].…”

Section: Mdma Analogues and Their Mdma-like Propertiesmentioning

confidence: 99%

MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology

Sáez-Briones

Hernández

2013

View full text Add to dashboard Cite

Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, “Ecstasy”) is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an “open mind state”, may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues.

show abstract

PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA

Cited by 14 publications

References 18 publications

Discriminative stimulus properties of α-ethyltryptamine optical isomers

Discriminative stimulus properties of α-ethyltryptamine optical isomers

Metabolism of Designer Drugs of Abuse

MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology

Contact Info

Product

Resources

About