• Cystometry;
  • enantiomer;
  • opioid;
  • monoamine reuptake;
  • morphine;
  • diuresis
  • (±)-Tramadol, a widely used analgesic, is a racemate stimulating opioid receptors and inhibiting reuptake of noradrenaline and serotonin, that is, pharmacological principles previously shown to influence rat micturition.

  • We studied both (±)-tramadol and its enantiomers in conscious Sprague–Dawley rats undergoing continuous cystometry. The effects of these agents were compared to those of morphine (μ-opioid receptor agonist) and tested after pretreatment with naloxone (μ-opioid receptor antagonist). Cystometries were evaluated before and after intravenous (i.v.), intraperitoneal (i.p.) and intrathecal (i.t.) drug administrations.

  • The most conspicuous effects of i.v. (±)-tramadol (0.1–10 mg kg−1) was an increase in threshold pressure and an increase in micturition volume.

  • These effects were mimicked by (+)-tramadol (0.1–5 mg kg−1 i.v.), whereas (−)-tramadol (5 mg kg−1 i.v.) did not influence threshold pressure and micturition volume.

  • The effects of (±)-tramadol 5 mg kg−1 on micturition volume were blocked by pretreatment with naloxone 0.3 mg kg−1. Morphine (0.3–10 mg kg−1 i.p.) increased threshold pressure but did not significantly increase micturition volume in doses not resulting in overflow incontinence.

  • (±)-Tramadol 10 mg kg−1 increased urine production, an effect blocked by desmopressin 25 ng kg−1.

  • (±)-Tramadol effectively inhibits micturition in conscious rats by stimulating μ-opioid receptors. A synergy between opioid receptor stimulation and monoamine reuptake inhibition may contribute to the micturition effects.

British Journal of Pharmacology (2003) 139, 741–748. doi:10.1038/sj.bjp.0705297