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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
[Chronopharmacology of tramadol in mice]
1Department of Pharmacology, Wannan Medical College, Wuhu 241001, China. liu8xiaoping@sina.com
Aim:
To investigate the influence of dosing time on acute toxicity, action and pharmacokinetics of tramadol in mice to find the circadian rhythms of the drug.
Methods:
Tramadol was given (i.p.) to mice at 08:00, 12:00, 16:00, 20:00, 24:00, 04:00 and the variations of their acute mortality, responses to hot plate and tail-pressing stimulation and pharmacokinetics were investigated.
Results:
Significant circadian rhythm was found for the acute toxicity of tramadol in mice and the highest mortality was found when the drug was administered in the middle dark phase. The rhythm of drug toxicity coincided nicely with the rhythm of plasma drug level. Tramadol effect was demonstrated to vary circadianly and the highest effect occurred in the late dark phase. Dosing-time dependent kinetics of tramadol was also found in mice.
Conclusion:
Significant circadian rhythm of the acute toxicity, action and pharmacokinetics was found in mice when tramadol was given at different times of the day.
Insights
Circadian rhythms significantly influence tramadol's acute toxicity and effects in mice. Optimal dosing times can enhance therapeutic outcomes and reduce adverse events.
Area of Science:
- Pharmacology
- Chronobiology
- Toxicology
Context:
- Circadian rhythms influence physiological processes and drug responses.
- Understanding temporal variations in drug pharmacokinetics and pharmacodynamics is crucial for optimizing treatment.
Purpose:
- To investigate the impact of dosing time on the acute toxicity, action, and pharmacokinetics of tramadol in mice.
- To identify potential circadian rhythms governing tramadol's effects and toxicity.
Summary:
- Tramadol administration at different times of day revealed significant circadian rhythms in its acute toxicity and effects in mice.
- Highest mortality occurred during the mid-dark phase, coinciding with peak plasma drug levels.
- Maximum analgesic effect was observed in the late dark phase, indicating time-dependent pharmacokinetics and pharmacodynamics.
Impact:
- Findings highlight the importance of considering circadian rhythms in tramadol dosing for improved efficacy and safety.
- This research provides a basis for chronopharmacological approaches to pain management and tramadol therapy.
