Document Detail


Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia.
MedLine Citation:
PMID:  23043631     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones.
EXPERIMENTAL APPROACH: The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines.
KEY RESULTS: At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α(1) -adrenoceptor and dopamine D(1) receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists.
CONCLUSIONS AND IMPLICATIONS: MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA.
Authors:
S E Shortall; A R Green; K M Swift; K C F Fone; M V King
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  168     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-25     Completed Date:  2013-07-16     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  966-77     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Antagonists / pharmacology
Alkaloids / pharmacology*
Animals
Body Temperature / drug effects
Body Temperature Regulation / drug effects*
Brain / drug effects,  metabolism
Catecholamines / blood,  metabolism
Dopamine Antagonists / pharmacology
Hypothermia / chemically induced*,  physiopathology
Male
Methamphetamine / analogs & derivatives*,  pharmacology
N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
Rats
Rats, Inbred Strains
Regional Blood Flow / drug effects
Chemical
Reg. No./Substance:
0/Adrenergic Antagonists; 0/Alkaloids; 0/Catecholamines; 0/Dopamine Antagonists; 44RAL3456C/Methamphetamine; 540EI4406J/cathinone; 8BA8T27317/mephedrone; KE1SEN21RM/N-Methyl-3,4-methylenedioxyamphetamine
Comments/Corrections

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