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Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.

Microwave heating is caused by the ability of the materials to absorb microwave energy and convert it to heat. This article represents a review on fundamentals of microwave heating and their interaction with materials for various applications in a comprehensive manner. Experimental studies of single, multimode, and variable frequency microwave processing were reviewed along with their applications. Modeling of microwave heating based on Lambert's law and Maxwell's electromagnetic field equations have also been reviewed along with their applications. Modeling approaches were used to predict the effect of resonances on microwave power absorption, the role of supports for microwave heating, and to determine the nonuniformity on heating rates. Various industrial applications on thermal processing have been reviewed. There is tremendous scope for theoretical and experimental studies on the athermal effects of microwaves. Some of the unresolved problems are identified and directions for further research are also suggested.

In rural tropical areas, patients frequently present with malaria and require urgent therapy. Facilities may not exist for parenteral drug administration, and oral dosing is precluded by obtundation or vomiting. In these circumstances, the rectal route of administration may allow initiation of antimalarial therapy while patients await transfer to hospital, a process that may take many hours.Artesunate (ARS) is a water-soluble hemisuccinate dihydroartemisinin (DHA) derivative being developed for the treatment of malaria and is particularly valuable against multidrugresistant infections (2, 13). ARS is currently formulated for administration by the oral and parenteral routes (3, 11). ARS suppositories (Rectocaps; 50 mg of artesunate; Mepha Pharmaceuticals Ltd.) Aesch-Basle, Switzerland) have recently undergone preliminary assessment in Gabonese children (8). However, formal bioavailability studies with this formulation are lacking. Circulating ARS is quickly converted to DHA by blood esterases and hepatic metabolism (14). As DHA is the principal antimalarial metabolite of ARS, the bioavailability of DHA was studied by comparing intrarectally (i.r.) and intravenously (i.v.) administered ARS in Ghanaian children with moderate malaria. High-performance liquid chromatography (HPLC) with electrochemical detection, currently the most precise and sensitive assay, was used to measure ARS and DHA levels. This crossover study was also designed to test the hypothesis that within the first 24 h there is no disease effect on the pharmacokinetics of ARS. These studies are critical to the design of larger (phase III-IV) studies seeking to use rectal ARS to reduce mortality from malaria. MATERIALS AND METHODS Study design description.This was an open, randomized, crossover comparison between i.v. ARS and ARS suppositories conducted on a pediatric research ward at Komfo-Anokye Teaching Hospital, Kumasi, Ghana, from August to October 1996. This study was approved by The Committee of Research, Publication and Ethics of the School of Medical Sciences, University of Science and Technology, Kumasi, Ghana, and the Review Board of the World Health Organization. A computer-generated randomization list allocating patients to one of three treatment categories was prepared (in permuted blocks of 12 patients). The treatment category for each patient was provided in an opaque sealed envelope opened only when a patient entered the study. Treatment categories were as follows: group I, i.r. ARS at 10 mg/kg of body weight, followed 12 h later by i.v. ARS at 2.4 mg/kg; group II, i.r. ARS at 20 mg/kg, followed 12 h later by i.v. ARS at 2.4 mg/kg; and group III, i.v. ARS at 2.4 mg/kg, followed 12 h later by i.r. ARS at 20 mg/kg. The doses of i.r. ARS were based on preliminary pharmacodynamic analysis of a similar study of i.r. ARS in Thai adults with moderate malaria (S. Looareesuwan, personal communication).Inclusion criteria. Patients aged 18 months to 7 years (inclusive) with a diagnosis of moderate Plasmodium falciparum malaria were eligible, pro...

Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self‐treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra‐performance liquid chromatography−tandem mass spectrometry (UPLC−MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7‐hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1–200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid‐rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%–38.7% w/w), paynantheine (0.3%–12.8% w/w), speciociliatine (0.4%–12.3% w/w), and speciogynine (0.1%–5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7‐hydroxymitragynine, isocorynantheidine) were also quantified (0.01%–2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.