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.