title: Actions of tramadol on micturition in awake, freely moving rats.
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.
authors.affiliation: Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden. Grünenthal GmbH, Aachen, Germany.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Pandita
authors.forename: Rikard
authors.initials: R
authors.lastname: Pehrson
authors.forename: Thomas
authors.initials: T
authors.lastname: Christoph
authors.forename: Elmar
authors.initials: E
authors.lastname: Friderichs
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D005260:Female; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics; D009068:Movement / Q000502:physiology*; D009270:Naloxone / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D014147:Tramadol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*; D014556:Urine; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
chemical_list: D017450:Receptors, Opioid, mu; D009270:Naloxone; D014147:Tramadol; D009020:Morphine; D003894:Deamino Arginine Vasopressin