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| Mitragyna speciosa is barely known in the United
States, but one of the most interesting plants we have
ever found... |
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| Kratom grows in the lush rainforests in the South of
Thailand, and has the unique position of being banned in
the country it is indigenous to...true story... |
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Mitragyna speciosa
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Studies on the synthesis and opioid agonistic activities of
mitragynine-related indole alkaloids: discovery of opioid agonists structurally
different from other opioid ligands.
Mitragynine (1) is a major alkaloidal component in the Thai traditional
medicinal herb, Mitragyna speciosa, and has been proven to exhibit analgesic
activity mediated by opioid receptors. By utilizing this natural product as a
lead compound, synthesis of some derivatives, evaluations of the
structure-activity relationship, and surveys of the intrinsic activities and
potencies on opioid receptors were performed with guinea pig ileum. The
affinities of some compounds for mu-, delta-, and kappa-receptors were
determined in a receptor binding assay. The essential structural moieties in the
Corynanthe type indole alkaloids for inducing the opioid agonistic activity were
also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine
pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists
with higher potency than morphine in the experiment with guinea pig ileum. In
addition, 2 induced an analgesic activity in the tail flick test in mice.
Mitragynine, an indole alkaloid from Thai folk medicine Mitragyna speciosa,
exerts agonistic effects on opioid receptors. Gastric acid secretion is proposed
to be regulated by opioid receptors in the central nervous system (CNS).
Previously, we reported the dual roles (inhibition via micro-opioid receptors
and stimulation via kappa-opioid receptors) of the opioid system in the central
control of gastric acid secretion. We investigated whether mitragynine affects
gastric acid secretion via opioid receptors in the CNS. Injection of mitragynine
(30 microg) alone into the lateral cerebroventricle did not have a significant
effect on basal gastric acid secretion in the perfused stomach of anesthetized
rats. Injection of mitragynine (3-30 microg) into the fourth cerebroventricle,
like morphine, inhibited 2-deoxy-D-glucose-stimulated gastric acid secretion.
The inhibitory effect of mitragynine (30 microg) was reversed by naloxone (100
microg). These results suggest that mitragynine has a morphine-like action on
gastric acid secretion in the CNS.
Reports of the various uses of Mitraynine in traditional
medicine in the countries of the South East Asia region (Jansen & Prast, 1988;
Suwanlert, 1974) spurred research into the
pharmacological aspects of its chemical constituents. More than twenty-five
alkaloids have been identified from this plant (Ikram, 1885) but of these the
major ones (in terms of % yield) are three indoles i.e. mitragynine,
speciogynine and paynanthine and two oxindoles i.e. mitraphylline and
speciofoline.
In a previous study (unpublished report) we had detected the analgesic property
of the crude alkaloidal extract using the hot-plate method of Ankier (1974) and
the tail-flick method of Sewell and Spencer (1976). The effect showed
similarities to analgesia caused by morphine but its effect was not antagonized
by Naloxone in the hot-plate test. This is interesting because although
paracetamol also exhibited a significant effect in the hot tail-flick test, our
additional experiment using the cold tail-flick test further separated the
analgesic efficacy of the alkaloidal extract and morphine from that of
paracetamol. The failure of paracetamol to exhibit antinociceptive effect in the
cold tail-flick test suggests that analgesia induced by morphine and the extract
is by a different pathway involving other mediators than that due to paracetamol.
This test also showed that 5 mg/kg of morphine is about equipotent to 200mg/kg
of the crude extract.
Other investigators have shown that the cold tail- flick method is a selective
method able to screen centrally acting opiate-fike analgesic agents, and is not
sensitive to analgesics acting peripherally, such as aspirin, or non-analgesic
drugs acting on the central nervous system, such as chlorpromazine (Pizziketti
et al., 1985).
by Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, Koyama F,
Matsumoto K, Moriyama T, Yamamoto LT, Watanabe K, Murayama T, Horie S.
Laboratory of Molecular Structure and Biological Function, Graduate School of
Pharmaceutical Sciences, Chiba University, Yayoi-cho, 1-33, Inage-ku, Chiba
263-8522, Japan. htakayam@p.chiba-u.ac.jp
Specific to Mitragyna speciosa
(Kratom):
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