Abstract

Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of its crude extracts, bioactive compounds and structurally modified derivatives have been examined in rodent models. This review aims to summarize the evidence on the antinociceptive effects of M. speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than crude extracts. Structurally modified derivatives of 7-hydroxymitragynine, such as MGM-9, MGM- 15, MGM-16, demonstrated superior antinociceptive effects compared to morphine. M. speciosa and its derivatives mainly act on the opioid receptor, but receptor subtypes specificity differs between each compound. The tolerance and adverse side effects of M. speciosa and its derivatives are similar with morphine. The affinity of MGM-9 on kappa-opioid receptor could potentially limit the effects of drug dependence. In conclusion, M speciosa derivatives can offer alternatives to morphine in controlling chronic pain. Structural modification of mitragynine and 7-hydroxymitragynine can generate compounds with higher potency and lesser side-effects. Human clinical trials are required to validate the use of these compounds in clinical setting.

Keywords: Analgesia, ketum, morphine, narcotic, nociception, opioid, pain.

Graphical Abstract