PMID- 1685125
OWN - NLM
STAT- MEDLINE
DCOM- 19920225
LR  - 20220311
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 200
IP  - 1
DP  - 1991 Jul 23
TI  - [3H]monoamine releasing and uptake inhibition properties of 
      3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues.
PG  - 9-16
AB  - The ability of several 3,4-methylenedioxymethamphetamine (MDMA) analogues to 
      inhibit the uptake of [3H]serotonin (5-HT), dopamine (DA) and norepinephrine (NE) 
      into synaptosomes was examined. In addition, the ability of the compounds to 
      inhibit the uptake of [3H]5-HT and DA into synaptosomes from rats pretreated with 
      reserpine (5 mg/kg i.p., 16 h pretreatment) was compared to control experiments. 
      All of the test compounds were found to be potent releasers of non-vesicular 5-HT 
      (the reserpine IC50 was significantly smaller than the control IC50). The range 
      of 5-HT inhibitory activity corresponds well to the small range of ED50 values of 
      the test compounds to substitute in drug discrimination experiments with animals 
      trained to discriminate MDMA or 
      S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane (S-MBDB) from saline. In 
      contrast, there was a wide range of potency for the inhibition of NE and DA 
      uptake. In addition, several of the analogues appeared to be pure uptake 
      inhibitors of DA while others were found to be releasers of non-vesicular DA. 
      Several of the compounds were very selective for 5-HT over DA or NE uptake 
      inhibition, including 3-methoxy-4-methylamphetamine (MMA) and 
      5-methoxy-6-methyl-2-aminoindan (MMAI). A correlation was noted between the 5-HT 
      neurotoxic potential of some of the test compounds and their relative ability to 
      induce a release of non-vesicular DA. The potential catechol metabolites of the 
      methylenedioxy-substituted compounds also showed potent monoamine releasing 
      properties, suggesting that metabolism may play a role in the neurotoxic actions 
      of some of these drugs. The present data support the hypothesis that 
      drug-stimulated non-vesicular 5-HT release is primarily responsible for the 
      discriminative cue of MDMA.
FAU - Johnson, M P
AU  - Johnson MP
AD  - Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal 
      Sciences, Purdue University, West Lafayette, IN 47907.
FAU - Conarty, P F
AU  - Conarty PF
FAU - Nichols, D E
AU  - Nichols DE
LA  - eng
GR  - DA-04578/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Designer Drugs)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - 8B1QWR724A (Reserpine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Designer Drugs/pharmacology
MH  - Dopamine/*metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Neurotransmitter Uptake Inhibitors/*pharmacology
MH  - Norepinephrine/*metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Regression Analysis
MH  - Reserpine/administration & dosage
MH  - Serotonin/*metabolism
MH  - Synaptosomes/*drug effects/metabolism
MH  - p-Chloroamphetamine/analogs & derivatives/*pharmacology
EDAT- 1991/07/23 00:00
MHDA- 1991/07/23 00:01
CRDT- 1991/07/23 00:00
PHST- 1991/07/23 00:00 [pubmed]
PHST- 1991/07/23 00:01 [medline]
PHST- 1991/07/23 00:00 [entrez]
AID - 0014-2999(91)90659-E [pii]
AID - 10.1016/0014-2999(91)90659-e [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1991 Jul 23;200(1):9-16. doi: 10.1016/0014-2999(91)90659-e.