AZD-5213 / AstraZeneca - LARVOL DELTA

Discovery of [18F]H3-2404 and [18F]H3-2405 as PET Probes for Imaging Histamine Subtype-3 Receptor (SNMMI 2025) - "Two H3R antagonists were designed based on the structure of AZD5213 (Figure 1A) and synthesized via condensation reactions and Suzuki coupling reactions (Figure 1B). Their inhibitory activities against H3R were evaluated via RBA conducted in 96-well plates. The cold standard compounds 1 (Ki = 10.2 nM) and 2 (Ki = 15.8 nM) exhibited moderate H3R binding affinities."

Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Novel Histamine Subtype 3 Receptor (H3R) PET Ligands for Brain Imaging (SNMMI 2025) - " A series of H3R antagonists, derived from AZD5213, were designed and synthesized... Fourteen novel H3R antagonists were synthesized via condensation reactions (Figure 1A) to explore SAR through three strategies: substituting the piperazine ring with C3-7 cycloalkyl groups, C1-4 alkyl groups, and polycycloalkanes. The H3R binding affinities were evaluated via [³H]AZ13153556 radioligand binding assays (RBA), employing both competition and saturation binding formats. The protocol consisted of incubating the radioligand, followed by vacuum filtration, washing steps, and measuring radioactivity with a MicroBeta counter."

CNS Disorders • Psychiatry

Discovery of 18F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor. (PubMed, Chembiochem) - "The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [18F]H3-2404 and [18F]H3-2405 are unsuitable as PET tracers for brain imaging of the H3 receptor, this study provides a valuable attempt for optimizing 18F labeled radiotracers based on AZD5213."

Journal • CNS Disorders

A Three-Way Crossover Study of Pregabalin, Placebo and the Histamine 3 Receptor Inverse Agonist AZD5213 in Combination with Pregabalin in Subjects with Painful Diabetic Neuropathy and Good Pain-Reporting Ability. (PubMed, Clin J Pain) - "The training of study subjects in pain reporting and subsequent enrichment with good pain reporters also did not enable the robust detection of efficacy of pregabalin relative to placebo in a small sample size. Further work is required before recommending the use of "connoisseur" subjects in future neuropathic pain studies."

Clinical • Combination therapy • Journal • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder (clinicaltrials.gov) - P2; N=29; Completed; Sponsor: AstraZeneca; Active, not recruiting -> Completed

Trial completion • Biosimilar

Development of [carbonyl-11C]AZ13198083, a novel histamine type-3 receptor radioligand with favorable kinetics. (PubMed, ACS Chem Neurosci) - "...To address this, we herein report the development of three novel candidate HR radioligands, namely, [ carbonyl-C]AZ13153556 ([ carbonyl-C]4), [ carbonyl-C]AZD5213([ carbonyl-C]5), and [ carbonyl-C]AZ13198083 ([ carbonyl-C]6), and their subsequent preclinical evaluation in nonhuman primates (NHP)...After pre-treatment or displacement with 5 (0.1 mg/mg), a uni-form low distribution of radioactivity across the NHP brain was observed. Collectively, this work demonstrates that [carbonyl-11C]6 is a promising candidate for H3R imaging in human subjects."

Journal