Suppressive Effect of Mitragynine on the 5-Methoxy-N,N-dimethyltryptamine-Induced Head-Twitch Response in Mice

Intrahepatic Cholestasis Following Abuse of Powdered Kratom (Mitragyna speciosa)

“…Corynantheidine also binds at μ-receptors but acts as a functional antagonist since it does not activate this receptor [8]. In addition to the opioid receptor-mediated effects, there are conflicting data on the effect of mitragynine on α 2 and HT 2A receptors [12][13][14]. Kratom is often said to have coca-like effects (first described in 1932 [15]), but except the increased ability to work, there is little evidence for amphetamine-like effects and the possible pharmacological mechanisms remain unclear.…”

Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna speciosa

“…Thus, this simple indole alkaloid could also be derived from strictosidine or related compounds, such as common monoterpenoid indole alkaloids. 21) By fragmentation of the aglucone of strictosamide (33) or that of vincoside lactam (34), the C4 unit was eliminated and subsequent oxidation (aromatization) of the D-ring produced nauclefidine (31). To prove this structure, the total synthesis of 31 was carried out.…”

“…32) An investigation of the effects of mitragynine (1) on the head-twitch response induced by 5-methoxy-N,N-dimethyltryptamine in mice indicated that the stimulation of postsynaptic a2-adrenoceptor, the blockade of 5-HT 2A receptors, or both, are involved in the suppression of 5-HT 2A receptor mediated head-twitch response by mitragynine. 33) In addition, it was suggested that antinociception caused by i.c.v. administration of mitragynine is dominantly mediated by m-and d-opioid receptor subtypes, and that the selectivity of mitragynine for the supraspinal opioid receptor subtypes differs from that of morphine in mice.…”

Formation of an Unusual Dimeric Compound by Lead Tetraacetate Oxidation of a Corynanthe-Type Indole Alkaloid, Mitragynine.

“…

In the recent chemical [1][2][3][4][5][6][7][8][9] and pharmacological [10][11][12][13][14][15] studies on the Rubiaceous plant, Mitragyna speciosa, [16][17][18][19][20] which has been traditionally used in tropical areas as a substitute for opium, 21) we have found that mitragynine (1), a major Corynanthe-type indole alkaloid of this plant, exhibited potent analgesic activity mediated by m-and d-opioid receptors.

22)Further, 7-hydroxymitragynine (3), 23) an oxidative derivative of 1, was found as a novel opioid agonist with higher potency than that of morphine.24) This remarkable opioid ligand was prepared from mitragynine (1) by conventional procedure, i.e., oxidation of 1 with lead tetraacetae [Pb(OAc) 4 ] followed by alkaline hydrolysis of the resultant 7-acetoxyindolenine (2). In investigating the first oxidation step in detail, we found a structurally and mechanistically novel dimerization product, as described in this publication.

Results and Discussion

In general, 7-acetoxyindolenine derivatives are prepared from the corresponding indoles by oxidation with Pb(OAc) 4 .

…”

“…In the recent chemical [1][2][3][4][5][6][7][8][9] and pharmacological [10][11][12][13][14][15] studies on the Rubiaceous plant, Mitragyna speciosa, [16][17][18][19][20] which has been traditionally used in tropical areas as a substitute for opium, 21) we have found that mitragynine (1), a major Corynanthe-type indole alkaloid of this plant, exhibited potent analgesic activity mediated by m-and d-opioid receptors.…”