Tramadol inhibits rat detrusor overactivity caused by dopamine receptor stimulation.
OBJECTIVE
In patients with Parkinson's disease an imbalance between stimulatory D2-like receptors and inhibitory D1-like receptors may contribute to detrusor overactivity. Apomorphine, which stimulates D1-like and D2-like dopamine receptors, induces detrusor overactivity in rats. Tramadol is an analgesic drug that stimulates opioid receptors and inhibits reuptake of serotonin and noradrenaline. To evaluate a potentially inhibitory effect of tramadol the drug was given to rats with apomorphine induced detrusor overactivity.


METHODS
Female Sprague-Dawley rats were used. During anesthesia catheters were introduced into the bladder dome, femoral vein and subcutaneously (SC). Three days later the rats were placed in a metabolism cage and voiding was stimulated by infusing saline into the bladder. Micturition parameters were recorded and compared after the administration of apomorphine and tramadol or vehicle. Desmopressin was given as pretreatment to suppress the diuresis produced by tramadol.


RESULTS
While 30 microg kg-1 apomorphine SC was devoid of effect, 60 and 100 microg kg-1 apomorphine SC induced a transient detrusor overactivity. Tramadol (1 mg kg-1) was without effect but 5 and 10 mg kg-1 tramadol intravenously attenuated the effects of apomorphine, while inducing prominent diuresis. Pretreatment with desmopressin, which did not alter cystometry or the effects of apomorphine, abolished diuresis. In these rats 5 and 10 mg kg-1 tramadol intravenously abolished the overactivity caused by apomorphine SC.


CONCLUSIONS
Tramadol effectively suppresses apomorphine induced detrusor overactivity in doses shown to have analgesic activity. Hence, tramadol may provide an approach to treat lower urinary tract disorders in which dopamine receptor activation is involved.
Pehrson
Rikard
R
Department of Clinical Pharmacology, Institute for Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden.
Andersson
Karl-Erik
KE
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D014147:Tramadol / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D014147:Tramadol; D001058:Apomorphine