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Analgesic Effects of Tramadol in Combination with Adjuvant Drugs: An Experimental Study in Rats

Background: Tramadol is often coadministered subcutaneously with adjuvants to treat pain, nausea/vomiting, dyspnea and delirium in cancer patients. The aim of the study was to investigate analgesia of tramadol coadministered with adjuvants in rats. Materials and Methods: Male rats (Wistar race) received a single tramadol dose separately (0.45 mg/kg) or tramadol with haloperidol (0.45 mg/kg), midazolam (0.3 mg/kg), levomepromazine (0.35 mg/kg), metoclopramide (1.0 mg/kg), hyoscine butylbromide (1.7 mg/kg) or ketamine (0.3 mg/kg) as a single subcutaneous injection. Analgesia was measured by a tail flick test after 15, 30, 60 and 90 min of drug administration. Results: Tramadol analgesia was enhanced with haloperidol (30, 60 and 90 min) and with midazolam (60 and 90 min). Tramadol with levomepromazine (30, 60 and 90 min) and tramadol with metoclopramide (30 and 90 min) attenuated tramadol analgesia. Tramadol with hyoscine butylbromide and tramadol with ketamine did not change tramadol analgesia. Conclusions: Significant changes in tramadol analgesia after the administration of different adjuvants could be demonstrated in this experimental single-dose study. Future clinical trials have to further explore the benefits of these drug combinations.