Effects of lisinopril, captopril and losartan alone or in combination with morphine in light tail flick analgesic test

There are controversial reports about the effect of captopril on pain modulation. Also while captopril may potentiate morphine analgesia, enalapril has not such an effect and interaction of morphine with angiotensin II receptor antagonists and other angiotensin converting enzyme inhibitors has not been studied yet. Therefore, this study was designed to assess the effect of captopril, lisinopril and losartan on pain sensation and the possible modifying effect of these drugs on morphine antinociception. Male Swiss mice (25-35 g) in groups of 6 animals per each received vehicle (10 ml/kg), captopril (20 mg/kg), lisinopril (10 mg/kg) and losartan (10 mg/kg) alone or in combination with morphine (5 mg/kg, i.p.) and analgesic response was assessed using light tail flick test. Reaction latencies to a light beam were recorded at 15 minute intervals until 2 hours. The maximum possible analgesic effect was calculated and compared. Lisinopril and captopril when administered alone could not change the pain response but losartan per se induced a hyperalgesic state. Pretreatment with captopril potentiated morphine analgesic response and losartan and lisinopril did not modify morphine analgesia. It is concluded that although angiotensin converting enzyme inhibitors have the same mechanism of action on renin-angiotensin system but they do not have the same interaction with morphine. Also since losartan, an antagonist of angiotensin receptor type 1 did not alter morphine response, it seems that these receptors are not involved in captopril potentiation of morphine analgesia.