Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex.
BACKGROUND
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.
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.
Cédric M
CM
Hysek
Matthias E
ME
Liechti
D000322:Adrenergic Agonists / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D000339:Affect / Q000187:drug effects; D001337:Autonomic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001833:Body Temperature Regulation / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003000:Clonidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D017292:Doxazosin / Q000494:pharmacology*; D000068736:Duloxetine Hydrochloride; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008027:Light; D008297:Male; D015877:Miosis / Q000503:physiopathology / Q000517:prevention & control; D009025:Morpholines / Q000494:pharmacology*; D015878:Mydriasis / Q000139:chemically induced / Q000503:physiopathology; D009184:Mydriatics / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D011930:Reaction Time / Q000187:drug effects; D000077593:Reboxetine; D020127:Recovery of Function; D012025:Reflex, Pupillary / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D055815:Young Adult
D000322:Adrenergic Agonists; D018759:Adrenergic Uptake Inhibitors; D058647:Adrenergic alpha-2 Receptor Agonists; D001337:Autonomic Agents; D002227:Carbazoles; D000077261:Carvedilol; D003000:Clonidine; D018765:Dopamine Uptake Inhibitors; D017292:Doxazosin; D000068736:Duloxetine Hydrochloride; D009025:Morpholines; D009184:Mydriatics; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011412:Propanolamines; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes