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J Pharm Pharmacol. 2016 Sep;68(9):1170-6. doi: 10.1111/jphp.12578. Epub 2016 Jun 23.

Synergistic analgesic effect of propofol-alfentanil combination through detecting the inhibition of cAMP signal pathway.

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Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.



The study aims to investigate the possible mechanism of the synergistic analgesic effect of propofol-alfentanil combination.


The synergistic analgesic effects of propofol-alfentanil combination in Sprague-Dawley (SD) rats were analysed through the von Frey test. Then, we examined the activity of phospholipase C (PLC) and the intracellular levels of Ca(2+) and adenosine 3', 5'cyclic monophosphate (cAMP) in primary neuronal cells of fetal SD rats. We detected the intracellular Ca(2+) concentration by fluorescence and flow cytometry. The PLC activity of the primary neuronal cells was assayed using the EnzChek(®) Direct Phospholipase C Assay Kit. The cAMP content of the cells was assayed using the cAMP Direct Immunoassay Kit (Fluorometric).


Both propofol and alfentanil treatments depressed cAMP levels and PLC activity, but propofol-alfentanil combination decreased these parameters to a greater extent than alfentanil treatment alone. Propofol and alfentanil both inhibited Ca(2+) channel, but propofol-alfentanil combination suppressed this channel to a greater extent than alfentanil treatment alone. Fluorescent image analysis revealed that both propofol and alfentanil reduced the intracellular levels of Ca(2+) , and propofol-alfentanil combination showed weaker signals than alfentanil alone. Propofol-alfentanil combination significantly reduced intracellular Ca(2+) level, cAMP level and PLC activity.


Propofol and alfentanil exert synergistic analgesic effects through the adenylyl cyclase pathway.


synergistic analgesic mechanism

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