AZD9272 / Takeda - LARVOL DELTA

Microtransplantation of native synaptic mGluR5 receptors into Xenopus oocytes. (Neuroscience 2022) - "However, antagonism of mGluR5 with 100 μM AZD 9272 showed a reduction of metabotropic currents elicited by ACPD and glutamate. Finally, we confirmed expression of both mGluR1 and mGluR5 in native synaptosomes by immunoblots, where we found protein enhancement in the isolated synaptosomes when compared to rat cortex whole tissue lysate. These results demonstrate the merit of native synaptosomes and their microtransplantation for the study of mGluR5’s contribution to metabotropic glutamate signaling, which has been linked with several neurological disorders such as Alzheimer’s disease, schizophrenia, and addiction."

Alzheimer's Disease • CNS Disorders • Psychiatry • Schizophrenia

Microtransplantation of Postmortem Native Synaptic mGluRs Receptors into Xenopus Oocytes for Their Functional Analysis. (PubMed, Membranes (Basel)) - "Since both mGluR1 and mGluR5 belong to Group 1 mGluRs, further investigation revealed that mGluR1 antagonism with LY 456236 has little effect on metabotropic oscillations, while mGluR5 antagonism with 100 µM AZD 9272 has significant reduction of metabotropic currents elicited by ACPD and glutamate. We confirmed the expression of mGluR1 and mGluR5 in native synaptosomes by immunoblots, both of which are enhanced when compared to their counterpart proteins in rat cortex tissue lysates. Finally, these results demonstrate the merit of using microtransplantation of native synaptosomes for the study of mGluRs and the contribution of mGluR5 to the metabotropic glutamate signaling, providing a better tool for the understanding of the role of these receptors in neurological disorders."

Journal • CNS Disorders • Transplantation

Effects of sevoflurane anaesthesia on radioligand binding to monoamine oxidase-B in vivo. (PubMed, Br J Anaesth) - "Sevoflurane anaesthesia inhibited radioligand binding to MAO-B in the primate brain. The observation of lower MAO-B binding at clinically relevant concentrations of sevoflurane warrants further exploration of the potential role of MAO-B related mechanisms in regulation of systemic blood pressure during anaesthesia."

Journal • Preclinical • Anesthesia

Safety evaluation of the mGluR5 antagonists AZD9272, AZD2066 AND AZD2516 in healthy volunteers and patients with neuropathic pain or major depressive disorder (WCP 2012) - Presentation time: Tuesday, August 28; 9:45 am; P1, N=116; In healthy volunteers the CNS-related AEs increased in frequency with increasing dose and were found to be subject to tolerance development in the AZD2066 multiple ascending dose (MAD) study; AEs were more common among those receiving active drug compared to placebo

P1 data • Pain

Synthesis, biodistribution and radiation dosimetry of a novel mGluR5 radioligand: [18F]AZD9272. (PubMed, ACS Chem Neurosci) - "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 [18F]AZD9272 could be used as an improved tool for quantitative assessment and characterization of AZD9272 binding sites in human brain by using PET."

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The pro-psychotic metabotropic glutamate receptor compounds fenobam and AZD9272 share binding sites with monoamine oxidase-B inhibitors in humans. (PubMed, Neuropharmacology) - "The findings are consistent with the hypothesis that both fenobam and AZD9272 bind to the MAO-B, which may be of relevance for understanding the mechanism of the psychosis-like adverse events reported for these compounds. Such understanding may serve as a lead to generate new models for the pathophysiology of psychosis."

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