Background/Aim. It is known that bile acids improve the absorption,
bioavailability and pharmacodynamic characteristics of some drugs. Morphine
analgesia is produced by activation of opioid receptors within the central
nervous system (CNS) at both spinal and supraspinal levels. Since a morphine
molecule contains 3 polar groups and therefore hard to transfer through the
blood-brain barrier, the aim of the study was to examine the potential
influence of bile acids derivates, namely sodium salt of monoketocholic acid
(MKH-Na) and methyl ester of monoketocholic acid (MKH-Me), on analgesic
effect of morphine. Methods. White male mice of NMRI-Haan strain, with body
weight of 20-24 g, were used in this study. The analgesic effect of morphine
(administered by subcutaneous and intramuscular route in a dose of 2 mg/kg),
with and without pretreatment with MKH-Na (4 mg/kg) and MKH-Me (4 mg/kg) was
estimated by the hot plate method. Results. Administration of MKH-Me prior to
subcutaneous administration of morphine increased the morphine analgesic
effect but the increase was not statistically significant. At the same time
administration of MKH-Na did not affect morphine analgesic effect. The
analgesic effect of morphine increased when administered intramuscularly 20
min after MKH-Me administration. When compared with the group of animals
treated only with morphine, a statistically significant increase in analgesic
effect was detected 10, 30, 40 and 50 min after morphine administration (p <
0.05). Pretreatment with MKH-Na did not affect morphine analgesic effect.
Conclusion. According to the results of this study it can be presumed that
after intramuscular morphine administration methyl ester of monoketocholic
acid increases morphine transport into the central nervous system and
consequently the analgesic effect, as well. Further research on bile
acids-morphine interaction both in vitro and in vivo is necessary to
completely elucidate the mechanism of this interaction and increase in the
morphine analgesic effect.