paynantheine and mitragynine

Kratom,

Topics: Alkaloids; Animals; Indole Alkaloids; Indoles; Male; Mitragyna; Molecular Structure; Oxindoles; Plant Preparations; Rats; Rats, Sprague-Dawley; Secologanin Tryptamine Alkaloids; Spiro Compounds

Kratom alkaloids have mostly been evaluated for their opioid activity but less at other targets that could contribute to their physiological effects. Here, we investigated the in vitro and in vivo activity of kratom alkaloids at serotonin receptors (5-HTRs). Paynantheine and speciogynine exhibited high affinity for 5-HT

Topics: Analgesics; Animals; Behavior, Animal; Female; HEK293 Cells; Humans; Male; Nociceptive Pain; Rats, Sprague-Dawley; Receptors, Serotonin; Secologanin Tryptamine Alkaloids

Mitragynine (MG) is the principal psychoactive alkaloid in kratom. The drug produces a variety of dose-dependent effects that appeal to recreational drug users and individuals seeking therapeutic benefits in the absence of medical supervision. In light of documented intoxications, hospitalizations and fatalities, MG and other alkaloids from Mitragyna speciosa are of growing importance to the forensic toxicology community. However, the chemical stability of these compounds has not been thoroughly described. In this report, the stability of MG, 7-hydroxymitragynine (MG-OH), speciociliatine (SC), speciogynine (SG) and paynantheine (PY) are investigated. Short-term stability of the Mitragyna alkaloids was determined over a range of pH (2-10) and temperature (4-80°C) over 8 hours. Liquid chromatography--quadrupole/time-of-flight mass spectrometry was used to estimate half-lives and identify degradation products where possible. The stability of MG and other alkaloids was highly dependent on pH and temperature. All of the Mitragyna alkaloids studied were acid labile. Under alkaline conditions, MG undergoes chemical hydrolysis of the methyl ester to produce 16-carboxymitragynine. MG-OH was the most unstable alkaloid studied, with significant drug loss at 8 hours experienced at temperatures of 40°C and above. No significant drug losses were observed for MG in aqueous solution (pH 2-10) at 4, 20 or 40°C. Diastereoisomers of MG (SC and SG) demonstrated even greater stability. These findings are discussed within the context of the identification of Mitragyna alkaloids in toxicological specimens.

Topics: Alkaloids; Chromatography, Liquid; Drug Stability; Forensic Toxicology; Humans; Hydrogen-Ion Concentration; Indole Alkaloids; Mitragyna; Oxindoles; Plant Extracts; Secologanin Tryptamine Alkaloids

The pharmacologically interesting indole alkaloids (-)-mitragynine, (+)-paynantheine and (+)-speciogynine were synthesised in nine steps from 4-methoxytryptamine by a route featuring (i) an enantioselective thiourea-catalysed Pictet-Spengler reaction, providing the tetrahydro-β-carboline ring and (ii) a Pd-catalysed Tsuji-Trost allylic alkylation, closing the D-ring.

Topics: Catalysis; Chemistry Techniques, Synthetic; Indole Alkaloids; Oxindoles; Secologanin Tryptamine Alkaloids; Thiourea