Publications by authors named "Andrew Biggerstaff"

Multiple sclerosis is an autoimmune disease characterised by demyelination in the central nervous system. The cuprizone-induced demyelination model is often used in mice to test novel treatments for multiple sclerosis. However, despite significant demyelination, behavioural deficits may be subtle or have mixed results depending on the paradigm used.

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Article Synopsis
  • GABAkines are positive allosteric modulators of GABA receptors, used to treat conditions like anxiety, epilepsy, and sleep disorders; however, the development of new GABAkines had slowed down due to safety and side-effect concerns.
  • Recently, there has been renewed interest and progress in bringing new GABAkines to market, with the FDA approving brexanolone for post-partum depression in 2019 and several others currently in clinical development.
  • KRM-II-81 is highlighted as a promising new GABAkine with potential effectiveness against pharmacoresistant epilepsy, traumatic brain injury, and neuropathic pain, showing low sedation, no tolerance development, and anxiolytic and antidepressant-like
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In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been highlighted as a key cellular mechanism to reduce the side effects of KOPr agonists.

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The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant . We assessed the antinociceptive, anti-cocaine, and side-effects of Mesyl Sal B.

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Declines in coral abundance have been linked to increased sedimentation at many locations across the world and at some of these locations there have been subsequent increases in sponge abundance. These shifts appear counterintuitive as sponges are suspension feeders and many rely on photosymbionts for carbon. At a sedimented reef in Indonesia (Wakatobi) corals have declined and the photoautotrophic sponge Lamellodysidea herbacea is now abundant.

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Previous structure-activity studies on the neoclerodane diterpenoid salvinorin A have demonstrated the importance of the acetoxy functionality on the A-ring in its activity as a κ-opioid receptor agonist. Few studies have focused on understanding the role of conformation in these interactions. Herein we describe the synthesis and evaluation of both flexible and conformationally restricted compounds derived from salvinorin A.

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Changes in sediment input to marine systems can influence benthic environments in many ways. Sponges are important components of benthic ecosystems world-wide and as sessile suspension feeders are likely to be impacted by changes in sediment levels. Despite this, little is known about how sponges respond to changes in settled and suspended sediment.

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Sponges are important for maintaining ecosystem function and integrity of marine and freshwater benthic communities worldwide. Despite this, there has been no assessment of their current global conservation status. We assessed their status, accounting for the distribution of research effort; patterns of temporal variation in sponge populations and assemblages; the number of sponges on threatened species lists; and the impact of environmental pressures.

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