Actions of tramadol on micturition in awake, freely moving rats.
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.
Pandita
Raj Kumar
RK
Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden. Grünenthal GmbH, Aachen, Germany.
Pehrson
Rikard
R
Christoph
Thomas
T
Friderichs
Elmar
E
Andersson
Karl-Erik
KE
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
D017450:Receptors, Opioid, mu; D009270:Naloxone; D014147:Tramadol; D009020:Morphine; D003894:Deamino Arginine Vasopressin