Delving into the Latest Updates on AZD-5213 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

H3 receptor

Mechanism

H3 receptor inverse agonists(Histamine H3 receptor inverse agonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Alzheimer DiseaseMild cognitive disorder

Inactive Indication

Diabetic NeuropathiesPainTourette Syndrome

Originator Organization

AstraZeneca PLC

Active Organization

AstraZeneca, Inc.

Inactive Organization

AstraZeneca PLC

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H25N3O2

InChIKeyVCQZCDSEWSFTPO-SJORKVTESA-N

CAS Registry1119807-02-1

This is a 2-part study. In Part 1 of the study, subjects will undergo a pain reporting training program in which a painful stimulus will be applied to the subject's hand, and the subjects will be asked to report how painful the stimulus is. Over the course of the pain training sessions, feedback will be provided to the subject about how accurately they are reporting their degree of pain, relative to the amount of pressure stimulus applied to evoke pain. Those subjects who have adequate pain reporting ability will be asked to continue into Part 2 of the study in which 3 different blinded study drugs will be administered to each subject, in a crossover design to compare whether or not the study drugs improve pain associated with diabetic neuropathy.

Start Date01 Nov 2013

Sponsor / Collaborator

AstraZeneca PLC

NCT01904773 / CompletedPhase 2

A 6-month, Multicenter, Randomized, Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder

This is a two-part, randomized, multi-center, blinded study in adolescents with Tourette's Disorder. There will be an up to 21-day screening period in which subject eligibility will be determined. In Part 1 of the study, the safety, tolerability and pharmacokinetics of AZD5213 will be assessed during a 1- week period.
In Part 2 of the study, the safety, tolerability, and preliminary efficacy of two doses (depending on tolerability in Part 1 of the study) of AZD5213 and placebo will be assessed through six consecutive four-week crossover periods. Each subject will receive both AZD5213 and placebo. A follow-up vist will take place at 14 (±) 7 days following the last dose of study drug.

Start Date01 Aug 2013

Sponsor / Collaborator

AstraZeneca PLC

NCT01548287 / CompletedPhase 2

A Phase IIa Safety and Tolerability Study to Investigate the Effect on Sleep of 3 Doses of AZD5213 and Placebo in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment During 4 Weeks of Treatment, Placebo-Controlled

This is a study where AZD5213 or placebo is given to patients with Mild Alzheimer's Disease or Mild Cognitive Impairment in a blinded and random assignment. The main study objective is to estimate the relationship of sleep duration versus dose after 4 weeks of treatment.

Start Date01 Apr 2012

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with AZD-5213

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100 Translational Medicine associated with AZD-5213

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100 Patents (Medical) associated with AZD-5213

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3

Literatures (Medical) associated with AZD-5213

01 Jan 2021·The Clinical Journal of PainQ3 · MEDICINE

A 3-way Cross-over Study of Pregabalin, Placebo, and the Histamine 3 Receptor Inverse Agonist AZD5213 in Combination With Pregabalin in Patients With Painful Diabetic Neuropathy and Good Pain-reporting Ability

Q3 · MEDICINE

Article

Author: Katz, Nathaniel ; Raudibaugh, Karen ; Alexander, Robert C ; Spierings, Egilius L H

Objectives:In this study, patients with painful diabetic neuropathy were trained using an experimental pain paradigm in an attempt to enroll a subset of patients who are “pain connoisseurs” and therefore more able to discriminate between active and placebo treatments.Methods:AZD5213, a novel histamine H3 receptor inverse agonist+pregabalin, pregabalin, and placebo were then tested in a 3-period cross-over.Results:The study did not provide any evidence of clinical efficacy for AZD5213 when combined with pregabalin in the treatment of painful diabetic neuropathy.Discussion:The training of study patients in pain reporting and subsequent enrichment with good pain reporters also did not enable the robust detection of the efficacy of pregabalin relative to placebo in a small sample size. Further work is required before recommending the use of “connoisseur” patients in future neuropathic pain studies.

01 Jul 2013·International Journal of NeuropsychopharmacologyQ2 · MEDICINE

AZD5213: a novel histamine H3 receptor antagonist permitting high daytime and low nocturnal H3 receptor occupancy, a PET study in human subjects

Q2 · MEDICINE

ArticleOA

Author: Segerdahl, Märta ; Stenkrona, Per ; Jucaite, Aurelija ; Takano, Akihiro ; Jostell, Karl-Gustav ; Halldin, Christer ; Nyberg, Svante ; Boström, Emma

AbstractThe histamine H3 receptor represents an appealing central nervous system drug target due to its important role in the neurobiology of cognition and wake-sleep regulation. The therapeutic benefit of H3 antagonists/inverse agonists may be hampered by disruption of sleep that has been observed in humans with prolonged high H3 receptor occupancy (H3RO), extending into night-time. AZD5213 is a highly selective H3 antagonist (in vitro inverse agonist) developed to achieve a pharmacokinetic profile permitting circadian fluctuations of H3RO. Its efficacy has been demonstrated in rodent behavioural models of cognition. In human subjects, AZD5213 was safe and well tolerated following repeated doses (1–14 mg/d) and demonstrated a short (∼5 h) half-life. In this PET study H3RO was measured using the radioligand [11C]GSK189254 ([11C]AZ12807110) in seven young male volunteers following single doses of AZD5213 (0.05–30 mg). H3RO was calculated using the Lassen plot method. The plasma concentrations and the affinity constant (Ki,pl 1.14 nmol/l, corresponding to the plasma concentration required to occupy 50% of available receptors) were used to estimate the H3RO time-course. AZD5213 showed dose and concentration dependent H3RO ranging from 16 to 90%. These binding characteristics and the pharmacokinetic profile of AZD5213 indicate that high daytime and low night-time H3RO could be achieved following once daily oral dosing of AZD5213. Fluctuations of H3RO following circadian rhythm of the histamine system may be expected to reduce the risk of sleep disruption while maintaining daytime efficacy. AZD5213 may thus be an optimal compound to evaluate the clinical benefit of selective H3 antagonism in cognitive disorders.

ChemBioChem

Discovery of ¹⁸F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype‐3 Receptor

Article

Author: Collier, Lee ; Zhai, Chuangyan ; Yuan, Hongjie ; Zhou, Xin ; Schou, Magnus ; Zhao, Chunyu ; Liang, Steven H ; Dahl, Kenneth ; Gao, Yabiao ; Mühlfenzl, Kim S. ; Sun, Zhenkun ; Rong, Jian ; Song, Zhendong ; Ran, Chongzhao ; Patel, Jimmy S. ; Chen, Jiahui ; Elmore, Charles S. ; Zhang, Linqi ; Chaudhary, Ahmad ; Haider, Ahmed ; Li, Yinlong

AbstractThe histamine subtype 3 (H3) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H3 receptor. In this study, we synthesized and evaluated the binding effects of [18F]H3–2404 and [18F]H3–2405 by modifying the structure of AZD5213, a selective H3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. 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.

100 Deals associated with AZD-5213

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	US	AstraZeneca, Inc.	01 Jul 2013
Mild cognitive disorder	Phase 2	US	AstraZeneca, Inc.	01 Jul 2013
Diabetic Neuropathies	Preclinical	US	AstraZeneca PLC	01 Nov 2013
Pain	Preclinical	US	AstraZeneca PLC	01 Nov 2013
Tourette Syndrome	Preclinical	US	AstraZeneca PLC	01 Aug 2013