Actions of tramadol on micturition in awake, freely moving rats

Br J Pharmacol. 2003 Jun;139(4):741-8. doi: 10.1038/sj.bjp.0705297.

Abstract

1 (+/-)-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. 2 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 ( micro -opioid receptor agonist) and tested after pretreatment with naloxone ( micro -opioid receptor antagonist). Cystometries were evaluated before and after intravenous (i.v.), intraperitoneal (i.p.) and intrathecal (i.t.) drug administrations. 3 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. 4 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. 5 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. 6 (+/-)-Tramadol 10 mg kg(-1) increased urine production, an effect blocked by desmopressin 25 ng kg(-1). 7 (+/-)-Tramadol effectively inhibits micturition in conscious rats by stimulating micro -opioid receptors. A synergy between opioid receptor stimulation and monoamine reuptake inhibition may contribute to the micturition effects.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Deamino Arginine Vasopressin / administration & dosage
  • Deamino Arginine Vasopressin / pharmacokinetics
  • Drug Administration Routes
  • Female
  • Morphine / administration & dosage
  • Morphine / pharmacokinetics
  • Movement / physiology*
  • Naloxone / administration & dosage
  • Naloxone / pharmacokinetics
  • Rats
  • Rats, Inbred Strains
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / physiology
  • Stereoisomerism
  • Tramadol / administration & dosage
  • Tramadol / antagonists & inhibitors
  • Tramadol / pharmacokinetics*
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiopathology
  • Urination / drug effects*
  • Urine
  • Urodynamics / drug effects
  • Urodynamics / physiology

Substances

  • Receptors, Opioid, mu
  • Naloxone
  • Tramadol
  • Morphine
  • Deamino Arginine Vasopressin