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Miotic and subject-rated effects of therapeutic doses of tapentadol, tramadol, and hydromorphone in occasional opioid users

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Abstract

Rationale

Tapentadol is a novel analgesic that activates mu-opioid receptors and blocks norepinephrine reuptake. There is very little information available regarding the non-analgesic pharmacodynamic effects of tapentadol.

Objectives

This outpatient study evaluated the physiological, subject-rated, and performance effects of therapeutic doses of tapentadol compared to two control drugs in humans.

Methods

This double-blind, within-subject study examined the effects of oral placebo, tapentadol (25, 50, and 75 mg), tramadol (50, 100, and 150 mg), and hydromorphone (2, 4, and 6 mg). Nine occasional opioid users completed the study. Pharmacodynamic drug effects were measured before and for 6 h after drug administration.

Results

All three doses of the tested drugs produced comparable, time-dependent decreases in pupil diameter, but the effects were generally not dose dependent. The high dose of tapentadol, as well as all three doses of tramadol and hydromorphone, increased positive subject-rated effects (e.g., “Good Effects” and “Like the Drug”) as a function of time. Only tramadol increased negative subject-rated effects (e.g., “Bad Effects” and “Nauseous”); however, these were of low magnitude.

Conclusions

The highest tested dose of tapentadol produced a profile of positive effects comparable to that of hydromorphone, whereas tramadol produced positive and negative subject-rated effects. The mixed findings for tramadol are consistent with previous findings indicating that it has a distinct profile of effects relative to prototypic opioids. Future research should examine the effects of higher tapentadol doses, as well as the factors contributing to the different subject-rated profile of effects observed for tramadol relative to tapentadol and hydromorphone.

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Acknowledgments

This research was supported by grant number R01DA025649 from the National Institute on Drug Abuse (PI, William W. Stoops) and by departmental start-up funds awarded to William W. Stoops. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or NIH. The authors wish to thank the staff at the University of Kentucky Laboratory of Human Behavioral Pharmacology for their technical and medical assistance.

Conflict of interest

The authors declare no conflicts of interest relevant to this project.

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Authors and Affiliations

  1. Department of Behavioral Science, University of Kentucky College of Medicine, 140 Medical Behavioral Science Building, Lexington, KY, 40536-0086, USA

    William W. Stoops & Craig R. Rush

  2. Department of Psychology, University of Kentucky College of Arts and Sciences, Lexington, KY, USA

    William W. Stoops & Craig R. Rush

  3. Department of Psychiatry, University of Kentucky College of Medicine, Lexington, KY, USA

    Paul E. A. Glaser & Craig R. Rush

  4. Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA

    Paul E. A. Glaser

Authors
  1. William W. Stoops
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  2. Paul E. A. Glaser
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  3. Craig R. Rush
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Correspondence to William W. Stoops.

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Stoops, W.W., Glaser, P.E.A. & Rush, C.R. Miotic and subject-rated effects of therapeutic doses of tapentadol, tramadol, and hydromorphone in occasional opioid users. Psychopharmacology 228, 255–262 (2013). https://doi.org/10.1007/s00213-013-3031-y

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