Document Detail


Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex.
MedLine Citation:
PMID:  22700038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Pupillometry can be used to characterize autonomic drug effects.
OBJECTIVE: This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function.
METHODS: Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo-MDMA (125 mg), placebo-placebo, pretreatment-placebo, or pretreatment-MDMA using a crossover design.
RESULTS: MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function.
CONCLUSIONS: The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration-time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.
Authors:
Cédric M Hysek; Matthias E Liechti
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't     Date:  2012-06-15
Journal Detail:
Title:  Psychopharmacology     Volume:  224     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-04-29     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  363-76     Citation Subset:  IM    
Affiliation:
Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital Basel and University of Basel, Hebelstrasse 2, CH-4031 Basel, Switzerland.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00886886;  NCT00990067;  NCT01136278;  NCT01270672;  NCT01386177
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Agonists / pharmacology
Adrenergic Uptake Inhibitors / pharmacology
Adrenergic alpha-2 Receptor Agonists / pharmacology
Adult
Affect / drug effects
Autonomic Agents / blood,  pharmacokinetics,  pharmacology*
Body Temperature Regulation / drug effects
Carbazoles / pharmacology*
Clonidine / pharmacology*
Cross-Over Studies
Dopamine Uptake Inhibitors / pharmacology
Doxazosin / pharmacology*
Female
Hemodynamics / drug effects
Humans
Light
Male
Miosis / physiopathology,  prevention & control
Morpholines / pharmacology*
Mydriasis / chemically induced,  physiopathology
Mydriatics / blood,  pharmacokinetics,  pharmacology*
N-Methyl-3,4-methylenedioxyamphetamine / blood,  pharmacokinetics,  pharmacology*
Propanolamines / pharmacology*
Randomized Controlled Trials as Topic
Reaction Time / drug effects
Recovery of Function
Reflex, Pupillary / drug effects*
Serotonin Uptake Inhibitors / pharmacology
Thiophenes / pharmacology*
Time Factors
Young Adult
Chemical
Reg. No./Substance:
0/Adrenergic Agonists; 0/Adrenergic Uptake Inhibitors; 0/Adrenergic alpha-2 Receptor Agonists; 0/Autonomic Agents; 0/Carbazoles; 0/Dopamine Uptake Inhibitors; 0/Morpholines; 0/Mydriatics; 0/Propanolamines; 0/Serotonin Uptake Inhibitors; 0/Thiophenes; 0K47UL67F2/carvedilol; 4205-90-7/Clonidine; 42542-10-9/N-Methyl-3,4-methylenedioxyamphetamine; 74191-85-8/Doxazosin; 947S0YZ36I/reboxetine; O5TNM5N07U/duloxetine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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