Graduate Thesis Or Dissertation

 

Morphine-codeine interactions in rodents Public Deposited

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  • Rats given morphine-codeine combinations exhibited significantly increased hotplate reaction times compared with rats given an analgesic dose of one agent alone. Genera, species, sex, protein binding and metabolism were studied as possible implicating factors for the increased reaction times. Both male and female rats exhibited increased reaction time, and showed no difference in onset and duration of the effect. When both analgesic and nonanalgesic doses of one agent were given to rats concomitantly, the increased reaction time was not produced. Thus the administration of both drugs was necessary to produce the interaction. The increased reaction time was not related to the method of measuring reaction times, since the effect was demonstrated using both the tailflick and hotplate techniques. A difference between genera was demonstrated when the interaction could not be shown in mice. Both morphine and codeine had one primary binding site in 3% bovine serum albumin (BSA) solution. Morphine was bound in BSA solution and rat plasma 49 ± 5% and 54 ± 4%, respectively. Codeine was bound in BSA solution and rat plasma 59 ± 6% and 64 ± 5%, respectively. The presence of one drug in varied amounts did not significantly affect the binding characteristics of the other agent. The dialyzable percent of the administered dose of morphine or codeine was 24 ± 4% and 23 ± 5%, respectively. The presence of one drug did not affect the dialyzable fraction of the other drug when the two were administered to rats concomitantly. Analysis of morphine metabolism in presence of varied concentrations of codeine provided no evidence to support the idea that codeine might be interfering with morphine metabolism. The presence of varying amounts of morphine did not affect codeine metabolism. Since no free morphine could be measured after codeine incubation, there was no evidence to support the hypothesis that liberation of morphine could be responsible for the increased reaction time. The factors studied in this treatise did not determine a mechanism for the interaction, but pointed out a possible genera difference and defined the interaction more clearly.
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