PMID- 1982656
OWN - NLM
STAT- MEDLINE
DCOM- 19910617
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 191
IP  - 1
DP  - 1990 Nov 20
TI  - Behavioral, biochemical and neurotoxicological actions of the alpha-ethyl 
      homologue of p-chloroamphetamine.
PG  - 1-10
AB  - The present set of experiments was designed to examine the effects of extension 
      of the alpha-methyl of p-chloroamphetamine (PCA) to an alpha-ethyl. Therefore, 
      the alpha-ethyl homologue of PCA, 1-(4-chlorophenyl)-2-aminobutane (CAB), was 
      compared to PCA in a number of pharmacological assays. CAB was 2-fold less potent 
      than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), 
      and 5-fold less potent at inhibiting uptake of [3H]dopamine ([3H]DA). In drug 
      discrimination assays, CAB was approximately 3-fold less potent than PCA in 
      animals trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or its 
      alpha-ethyl homologue, S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine 
      (S-(+)-MBDB), from saline. Monitoring with in vivo microdialysis, 10 mg/kg of PCA 
      caused a large increase in extracellular DA and a significant decrease in 
      3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. In contrast, 11 mg/kg CAB 
      caused no increase and 22 mg/kg CAB caused only a slight increase in 
      extracellular DA. Both doses of CAB caused a decrease in extracellular DOPAC. The 
      potential 5-HT neurotoxicity of CAB was examined by measuring monoamine and 
      metabolite levels and [3H]paroxetine binding at one week following acute doses. A 
      10 mg/kg dose of PCA caused an 80% decrease in cortical and hippocampal 
      serotonergic markers, while an equimolar dose of CAB decreased only hippocampal 
      5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels. However, 22 mg/kg of CAB 
      produced a 20-40% decrease in all serotonergic markers. Thus, extension of the 
      alpha-alkyl significantly decreases the dopaminergic effects of PCA. The similar 
      decrease in relative 5-HT neurotoxicity and the decreased ability to alter 
      dopaminergic systems in vivo and in vitro supports the involvement of DA in the 
      neurotoxicity of PCA.
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 - Huang, X M
AU  - Huang XM
FAU - Oberlender, R
AU  - Oberlender R
FAU - Nash, J F
AU  - Nash JF
FAU - Nichols, D E
AU  - Nichols DE
LA  - eng
GR  - DA-04758/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 2275-64-1 (1-(4-chlorophenyl)-2-aminobutane)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/toxicity
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Biological Transport, Active/drug effects
MH  - Brain/drug effects/metabolism
MH  - Discrimination Learning/drug effects
MH  - Dopamine/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nervous System/*drug effects
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/metabolism
MH  - p-Chloroamphetamine/*analogs & derivatives/toxicity
EDAT- 1990/11/20 00:00
MHDA- 1990/11/20 00:01
CRDT- 1990/11/20 00:00
PHST- 1990/11/20 00:00 [pubmed]
PHST- 1990/11/20 00:01 [medline]
PHST- 1990/11/20 00:00 [entrez]
AID - 0014-2999(90)94090-K [pii]
AID - 10.1016/0014-2999(90)94090-k [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1990 Nov 20;191(1):1-10. doi: 10.1016/0014-2999(90)94090-k.