title: Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment.
abstract: BACKGROUND
  Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects.
  
  
  OBJECTIVE
  This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans.
  
  
  METHODS
  This inpatient, double-blind, randomized, within-subject study examined the effects of oral placebo, tramadol (87.5, 175, and 350 mg), and hydromorphone (4 and 16 mg; positive control) after 1 h pretreatment with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the study. Pharmacodynamic effects were measured before and for 7 h after initial drug administration.
  
  
  RESULTS
  Lower doses of tramadol and hydromorphone were generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced miosis and increased ratings of "Good Effects" and "Liking" but also increased ratings of "Bad Effects." Naltrexone reversed tramadol-induced physiological effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone only partially attenuated tramadol's positive subjective effects and actually enhanced several unpleasant subjective ratings.
  
  
  CONCLUSIONS
  Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol. High-dose tramadol produces a mixed profile of effects. These data suggest that both mu and non-mu opioid actions play a role in tramadol's subjective profile of action.
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, 140 Medical Behavioral Science Building, Lexington, KY 40536-0086, USA. william.stoops@uky.edu
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lofwall
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nuzzo
authors.forename: Lori B
authors.initials: LB
authors.lastname: Craig
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Siegel
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walsh
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D014147:Tramadol; D009271:Naltrexone; D004091:Hydromorphone