PMID- 35401275
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 13
DP  - 2022
TI  - Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated.
PG  - 863088
LID - 10.3389/fpsyt.2022.863088 [doi]
LID - 863088
AB  - At first glance, it appears there is little difference between the molecular 
      structures of methylenedioxymethamphetamine (MDMA), which has an N-methyl 
      attached to its amino group, and methylenedioxyamphetamine (MDA), a primary amine 
      that is recognized to have hallucinogenic activity. It is known from studies with 
      other hallucinogenic amphetamines that N-methylation of hallucinogenic 
      amphetamines attenuates or abolishes hallucinogenic activity. Nevertheless, MDMA 
      is biologically active and has a potency only slightly less than its MDA parent. 
      Importantly, it is the Ievo-isomer of hallucinogenic phenethylamines that is more 
      biologically active, whereas it is the dextro isomer of MDMA that is more active. 
      This reversal of stereochemistry for the activity of two very closely related 
      molecules is a very powerful clue that their mechanisms of action differ. 
      Finally, extension of the alpha-methyl of hallucinogenic amphetamines to an 
      alpha-ethyl moiety completely abolishes their hallucinogenic activity. 
      Ultimately, we extended the alpha-methyl group of MDMA to an alpha-ethyl to 
      afford a molecule we named (N-Methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) 
      that retained significant MDMA-like psychoactivity. Hence, there are three 
      structural features that distinguish MDMA from the hallucinogenic amphetamines: 
      (1) the N-methyl on the basic nitrogen, (2) the reversal of stereochemistry and, 
      (3) tolerance of an alpha-ethyl moiety as contrasted with the alpha-methyl of 
      hallucinogenic phenethylamines. Clearly, MDMA is distinct from classical 
      hallucinogenic phenethylamines in its structure, and its psychopharmacology is 
      also unique. Thus, in 1986 I proposed the name "Entactogen" for the 
      pharmacological class of drugs that includes 3,4-methylenedioxymethamphetamine 
      (MDMA) and other substances with a similar psychopharmacological effect. The name 
      is derived from roots that indicate that entactogens produce a "touching within." 
      Rather than having significant psychostimulant, or hallucinogenic effects, MDMA 
      powerfully promotes affiliative social behavior, has acute anxiolytic effects, 
      and can lead to profound states of introspection and personal reflection. Its 
      mechanism of action is now established as involving transport of MDMA by the 
      neuronal serotonin reuptake carrier followed by carrier-mediated release of 
      stored neuronal serotonin.
CI  - Copyright (c) 2022 Nichols.
FAU - Nichols, David E
AU  - Nichols DE
AD  - Division of Chemical Biology and Medicinal Chemistry, The University of North 
      Carolina at Chapel Hill, Chapel Hill, NC, United States.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220325
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC8990025
OTO - NOTNLM
OT  - MBDB
OT  - MDMA
OT  - entactogen
OT  - serotonin
OT  - serotonin transporter
COIS- The author declares that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/12 06:00
MHDA- 2022/04/12 06:01
PMCR- 2022/03/25
CRDT- 2022/04/11 05:27
PHST- 2022/01/26 00:00 [received]
PHST- 2022/03/01 00:00 [accepted]
PHST- 2022/04/11 05:27 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/04/12 06:01 [medline]
PHST- 2022/03/25 00:00 [pmc-release]
AID - 10.3389/fpsyt.2022.863088 [doi]
PST - epublish
SO  - Front Psychiatry. 2022 Mar 25;13:863088. doi: 10.3389/fpsyt.2022.863088. 
      eCollection 2022.