Effects of Mitragynine and a Crude Alkaloid Extract Derived from Mitragyna speciosa Korth. on Permethrin Elimination in Rats

Abstract

Detoxification and elimination of permethrin (PM) are mediated by hydrolysis via carboxylesterase (CES). Mitragyna speciosa (kratom) contains mitragynine (MG) and other bioactive alkaloids. Since PM and MG have the same catalytic site and M. speciosa is usually abused by adding other ingredients such as pyrethroid insecticides, the effects of MG and an alkaloid extract (AE) on the elimination of PM were investigated in rats. Rats were subjected to single and multiple pretreatment with MG and AE prior to receiving a single oral dose (460 mg/kg) of PM. Plasma concentrations of trans-PM and its metabolite phenoxybenzylalcohol (PBAlc) were measured. The elimination rate constant (kel) and the elimination half-life (t1/2 el) of PM were determined, as well as the metabolic ratio (PMR).A single and multiple oral pretreatment with MG and AE altered the plasma concentration-time courses of both trans-PM and PBAlc during 8–22 h, decreased the PMRs, delayed elimination of PM, but enhanced elimination of PBAlc. Results indicated that PM–MG or AE toxicokinetic interactions might have resulted from the MG and AE interfering with PM hydrolysis. The results obtained in rats suggest that in humans using kratom cocktails containing PM, there might be an increased risk of PM toxicity due to inhibition of PM metabolism and elimination.

Kratom: a dangerous player in the opioid crisis

“…This explains its analgesic effect and its role in ameliorating opioid withdrawal symptoms. The M. speciosa leaf extracts are its most effective part and have been shown to interact with the drug-metabolizing enzymes, showing the most potent inhibition on CYP2D6 activity [4,7]. …”

Ultrasound-assisted extraction conditions optimisation using response surface methodology from Mitragyna speciosa (Korth.) Havil leaves

“…M. speciosa has been applied as a traditional medicine to heal muscle fatigue and tiredness, as well as a herbal cure for a number of common sicknesses, such as diarrhoea, diabetes, coughing, and hypertension. Besides its similar function as an alternate substance for morphine or opium to cure drug addiction [22] , [23] , [24] , various studies have discovered that M. speciosa possesses various biological activities , such as anti-inflammation [23] , antinociceptive [23] , antioxidant [25] , [26] , and antimicrobial [26] . Apart from the well-known presence of alkaloids that exhibit significant bioactive functionalities, other phytochemicals, such as phenolic compounds from the crude extract, are also believed to contribute to the synergistic effect of the biological activities in M. speciosa .…”

Solid phase extraction method for determination of mitragynine in urine and its application to mitragynine excretion study in rats receiving caffeine

“…The concomitant use of kratom and CF may cause overstimulation or elevated blood pressure, so this should be avoided [1]. MG showed toxicokinetic interaction with permethrin [21]. A single and multiple oral pretreatment with MG and kratom alkaloid extract delayed the elimination of permethrin in rats probably by inhibition of its hydrolysis, and this may increase the risk of permethrin neurotoxicity in kratom users.…”