AIM OF STUDY: To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell.
METHOD AND MATERIALS: Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR.
RESULT: Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of mitragynine while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only.
CONCLUSION: These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine.
METHOD: A randomized controlled open-label study was performed at the cardiothoracic intensive care unit of Penang Hospital, Malaysia. A total of 28 patients who underwent cardiac surgeries were randomly assigned to receive either dexmedetomidine or morphine. Both groups were similar in terms of preoperative baseline characteristics. Efficacy measures included sedation scores and pain intensity and requirements for additional sedative/analgesic. Mean heart rate and arterial blood pressure were used as safety measures. Other measures were additional inotropes, extubation time and other concurrent medications.
RESULTS: The mean dose of dexmedetomidine infused was 0.12 [SD 0.03] μg kg⁻¹ h⁻¹, while that of morphine was 13.2 [SD 5.84] μg kg⁻¹ h⁻¹. Dexmedetomidine group showed more benefits in sedation and pain levels, additional sedative/analgesic requirements, and extubation time. No significant differences between the two groups for the outcome measures, except heart rate, which was significantly lower in the dexmedetomidine group.
CONCLUSION: This preliminary study suggests that dexmedetomidine was at least comparable to morphine in terms of efficacy and safety among cardiac surgery patients. Further studies with larger samples are recommended in order to determine the significant effects of the outcome measures.