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.

Building Information Modelling (BIM) is a technology with the potential to transform the construction industry, yet its proliferation remains stagnant. Existing research on BIM diffusion focuses on the industry, company, and project levels while disregarding the impact of perceptions at the individual level. This research aims to extend the Unified Theory of Acceptance and Use Technology (UTAUT) model to understand the perceptions that individuals have towards working with BIM. A survey was completed by 84 industry stakeholders and the results analysed against a modified UTAUT model that adds the variable of Attitude and employs moderators of Experience and Voluntariness. The results reveal that Performance Expectancy does not directly affect Behavioural Intention, signifying that BIM is perceived as an unrewarded addition to existing work processes. These findings evince the need to redefine strategies, policies, and incentive schemes in order to advance the acceptance of BIM in the U.K. and worldwide.

Ten indole and oxindole alkaloids (1–10) were isolated from the freshly collected leaves of Malaysian Mitragyna speciosa (Kratom). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data analysis. The spectroscopic data of mitragynine oxindole B (4) are reported herein for the first time. The spatial configuration of mitragynine oxindole B (4) was confirmed by single-crystal X-ray diffraction. Simultaneous quantification of the isolated alkaloids in the M. speciosa leaf specimens collected from different locations in the northern region of Peninsular Malaysia was also performed using UPLC-MS/MS. The oxindole alkaloids (1–4) and the indole alkaloid (10) were assessed for binding affinity at opioid receptors. Corynoxine (1) showed high binding affinity to μ-opioid receptors with a K i value of 16.4 nM. Further, corynoxine (1) was 1.8-fold more potent than morphine in rats subjected to a nociceptive hot plate assay. These findings have important implications for evaluating the combined effects of the minor oxindole alkaloids in the overall therapeutic activity of M. speciosa.

Multiple measures can enhance prescribing efficiency. Health authorities cannot rely on a 'spillover' effect from other classes in order to affect changes in physician prescribing habits.

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