Acs Chem Neurosci
-
The metabotropic glutamate receptor subtype mGluR5 has been proposed as a potential drug target for CNS disorders such as anxiety, depression, Parkinson's disease, and epilepsy. The AstraZeneca compound AZD9272 has previously been labeled with carbon-11 and used as a PET radioligand for mGluR5 receptor binding. The molecular structure of AZD9272 allows one to label the molecule with fluorine-18 without altering the structure. ⋯ Highest uptakes were seen in liver and small intestine, followed by brain and kidney. The estimated effective dose was around 0.017 mSv/MBq. 18F-AZD9272 shows suitable properties as a PET radioligand for in vivo imaging of binding in the primate brain. 18F-labeled AZD9272 offers advantages over 11C-AZD9272 in terms of higher image resolution, combined with a longer half-life. Moreover, based on the distribution and the estimated radiation burden, imaging of 18F-AZD9272 could be used as an improved tool for quantitative assessment and characterization of AZD9272 binding sites in the human brain by using PET.
-
The psychoactive plant kratom is a native plant to Southeast Asia, and its major bioactive alkaloid is mitragynine. Mitragynine exerts its analgesic properties by acting on the opioid receptors. One of its active metabolites, 7-hydroxymytraginine, is found to be 40 times more potent than mitragynine and 10 times more potent than morphine. ⋯ Kratom is currently marketed in the United States as a dietary or herbal supplement used to treat chronic pain, anxiety, and depression with over $207 million in annual sales in the United States alone. Here, we will review the traditional and medicinal uses of kratom along with the synthesis of its bioactive ingredients and their pharmacology, metabolism, and structure-activity relationships. The importance in society of this currently controversial substance will also be discussed.
-
Previous diffusion tensor imaging (DTI) research in mild traumatic brain injury (mTBI) patients only concentrated on a limited number of brain regions and a specific cognitive function. Thus, the study aimed to explore the association between DTI findings and cognitive function following mTBI using a meta-analysis. We conducted a search for articles exploring the associations between DTI findings and cognitive outcomes following mTBI published in English in databases (PubMed, Web of Science, EMBASE, Medline, and Google Scholar) before October 2019. ⋯ The study indicated that higher mean diffusivity (MD)/apparent diffusion coefficient (ADC) values in the external capsule (EC) were associated with worse memory. Additionally, higher MD/ADC values in the UF were associated with worse attention, processing speed, and working memory. The present study showed that better white matter integrity (higher FA, lower MD/ADC) might be associated with better cognitive function following mTBI.
-
Naringenin (2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one is a natural flavonoid found in fruits from the citrus family. Because (2S)-naringenin is known to racemize, its bioactivity might be related to one or both enantiomers. Computational studies predicted that (2R)-naringenin may act on voltage-gated ion channels, particularly the N-type calcium channel (CaV2.2) and the NaV1.7 sodium channel-both of which are key for pain signaling. ⋯ Naringenin had no effect on the nociceptive thresholds evoked by heat. Naringenin's reversed allodynia was in mouse models of postsurgical and neuropathic pain. Here, driven by a call by the National Center for Complementary and Integrative Health's strategic plan to advance fundamental research into basic biological mechanisms of the action of natural products, we advance the antinociceptive potential of the flavonoid naringenin.