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• W2079076407 abstract "Morphine is a gold standard analgesic commonly used to alleviate pain. However, its use is associated with unavoidable side effects including the risk for addiction. Peripherally administered loperamide lacks effect on the central nervous system as it is a substrate for the permeability glycoprotein (P-gp) efflux pump which blocks its entry into brain. However, when administered intrathecally, loperamide has been reported to produce analgesia. The present study investigates the mechanism of the central analgesic effect of loperamide. Adult male Sprague-Dawley rats were subjected to surgery for catheter placement. Following baseline testing, different groups of rats were administered fixed intrathecal doses (1 μg, 3 μg, 10 μg and 30 μg) of loperamide and morphine. Analgesia was compared employing Hargreaves paw withdrawal apparatus at 15 min, 30 min, 60 min, 90 min and 120 min. Additionally, CTOP, a specific mu-opioid receptor antagonist was co-administered with loperamide to examine the mu-opioid receptor mediated loperamide analgesia. Furthermore, nefiracetam, a calcium channel opener, was co-administered with loperamide or morphine to evaluate the involvement of Ca2+ channels in Loperamide showed an analgesic effect which was comparable to morphine. However, loperamide produced longer analgesia and the analgesic effect was significantly better at 42 h and 49 h compared to morphine. CTOP completely reversed loperamide analgesia. Though nefiracetam significantly reversed loperamide analgesia, it did not have any effect on morphine induced analgesia. Our findings suggest that loperamide administered intrathecally produces analgesia which is mediated through mu-opioid receptor and subsequent blockade of downstream calcium channels." @default.
• W2079076407 created "2016-06-24" @default.
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• W2079076407 date "2012-12-01" @default.
• W2079076407 modified "2023-09-26" @default.
• W2079076407 title "Antinociceptive effect of intrathecal loperamide: Role of mu-opioid receptor and calcium channels" @default.
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• W2079076407 doi "https://doi.org/10.1016/j.ejphar.2012.09.022" @default.
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