Delving into the Latest Updates on AVL-3288 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Compound 6 (N-(4-chlorophenyl)-α-[[(4-chloro-phenyl)amino]methylene]-3-methyl-5-isoxazoleacet-amide)

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Target

CHRNA7

Action

positive allosteric modulator

Mechanism

CHRNA7 positive allosteric modulator(Neuronal acetylcholine receptor protein alpha-7 subunit positive allosteric modulator)

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication

Central Nervous System DiseasesCognitive Dysfunction

Inactive Indication

Schizoaffective disorderSchizophrenia

Originator Organization

Anvyl Pharmaceuticals

Active Organization

University of California, Irvine

Inactive Organization

National Institute of Mental Health

University of Maryland BaltimoreAnvyl LLC

+ [1]

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC19H15Cl2N3O2

InChIKeyVMAKIACTLSBBIY-UHFFFAOYSA-N

CAS Registry917837-54-8

Single-center, randomized, double-blind, placebo-controlled, proof-of-principle study to evaluate potential cognitive benefits of a single oral dose of AVL-3288 (3 mg) in the presence and absence of transdermal nicotine (7 mg/24 hrs) in healthy non-smokers, while monitoring the safety and tolerability of AVL-3288.

Start Date01 May 2018

Sponsor / Collaborator

University of Maryland Baltimore

NCT02978599

/ CompletedPhase 1IIT

Double Blind, Two Dose, Cross-over Clinical Trial of the Positive Allosteric Modulator at the alpha7 Nicotinic Cholinergic Receptor AVL-3288 in Schizophrenia Patients

Single-center, outpatient, randomized, double-blind, placebo-controlled, 3-treatment-phase, cross-over study to evaluate the safety, tolerability and efficacy of two oral doses of AVL-3288 each compared to placebo, in patients with schizophrenia.

Start Date01 Nov 2016

Sponsor / Collaborator

The New York State Psychiatric Institute

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NCT01851603

/ TerminatedPhase 1IIT

Phase I, Single-center, Inpatient, Randomized, Double-blind, Placebo-controlled, Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profiles of Single Oral Doses of AVL-3288 (Anvylic-3288) Healthy Subjects.

This is a brief inpatient study to determine the safety of a new drug in healthy people.

Start Date01 Jun 2013

Sponsor / Collaborator

University of Colorado Denver

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100 Clinical Results associated with AVL-3288

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100 Translational Medicine associated with AVL-3288

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100 Patents (Medical) associated with AVL-3288

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28

Literatures (Medical) associated with AVL-3288

01 Aug 2024·Pharmacology Biochemistry and Behavior

Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation

Article

Author: Paykal, Gökçen ; Aykan, Utku ; Güvel, Muhammed Cihan ; Uluoğlu, Canan

OBJECTIVECaffeine and modafinil are used to reverse effects of sleep deprivation. Nicotinic alpha-7 receptor and AMPA receptor positive allosteric modulators (PAM) are also potential substances in this context. Our objective is to evaluate the effects of caffeine, modafinil, AVL-3288 (nicotinic alpha-7 PAM) and CX516 (AMPA receptor PAM) on cognition and mood in a model of sleep deprivation.METHODModified multiple platform model is used to sleep-deprive mice for 24 days, for 8 h/day. Vehicle, Modafinil (40 mg/kg), Caffeine (5 mg/kg), CX516 (10 mg/kg), and AVL3288 (1 mg/kg) were administered intraperitoneally daily. A cognitive test battery was applied every six days for four times. The battery that included elevated plus maze, novel object recognition, and sucrose preference tests was administered on consecutive days.RESULTSSleep deprivation decreased novel object recognition skill, but no significant difference was found in anxiety and depressive mood. Caffeine administration decreased anxiety-like behavior in short term, but this effect disappeared in chronic administration. Caffeine administration increased memory performance in chronic period. AVL group showed better memory performance in short term, but this effect disappeared in the rest of experiment. Although, in the modafinil group, no significant change in mood and memory was observed, anhedonia was observed in the chronic period in vehicle, caffeine and modafinil groups, but not in AVL-3288 and CX-516 groups.CONCLUSIONCaffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression.

01 Feb 2024·Experimental Neurology

Enhancing cognitive function in chronic TBI: The Role of α7 nicotinic acetylcholine receptor modulation

Article

Author: Placeres-Uray, Fabiola ; Gee, Kelvin W ; Johnstone, Timothy ; Hogenkamp, Derk ; Titus, David J ; Atkins, Coleen M ; Sangadi, Dinesh K ; Sangadi, Akhila

Traumatic brain injury (TBI) results in several pathological changes within the hippocampus that result in adverse effects on learning and memory. Therapeutic strategies to enhance learning and memory after TBI are still in the early stages of clinical development. One strategy is to target the α7 nicotinic acetylcholine receptor (nAChR), which is highly expressed in the hippocampus and contributes to the formation of long-term memory. In our previous study, we found that AVL-3288, a positive allosteric modulator of the α7 nAChR, improved cognitive recovery in rats after moderate fluid-percussion injury (FPI). However, whether AVL-3288 improved cognitive recovery specifically through the α7 nAChR was not definitively determined. In this study we utilized Chrna7 knockout mice and compared their recovery to wild-type mice treated with AVL-3288 after TBI. We hypothesized that AVL-3288 treatment would improve learning and memory in wild-type mice, but not Chrna7^-/- mice after TBI. Adult male C57BL/6 wild-type and Chrna7^-/- mice received sham surgery or moderate controlled cortical impact (CCI) and recovered for 3 months. Mice were then treated with vehicle or AVL-3288 at 30 min prior to contextual fear conditioning. At 3 months after CCI, expression of α7 nAChR, choline acetyltransferase (ChAT), high-affinity choline transporter (ChT), and vesicular acetylcholine transporter (VAChT) were found to be significantly decreased in the hippocampus. Treatment of wild-type mice at 3 months after CCI with AVL-3288 significantly improved cue and contextual fear conditioning, whereas no beneficial effects were observed in Chrna7^-/- mice. Parietal cortex and hippocampal atrophy were not improved with AVL-3288 treatment in either wild-type or Chrna7^-/- mice. Our results indicate that AVL-3288 improves cognition during the chronic recovery phase of TBI through modulation of the α7 nAChR.

01 Jan 2021·Behavioural Brain ResearchQ3 · PSYCHOLOGY

α7 nicotinic receptor agonist and positive allosteric modulators differently improved schizophrenia-like cognitive deficits in male rats

Q3 · PSYCHOLOGY

Article

Author: Sirvanci, Serap ; Aricioglu, Feyza ; Unal, Gokhan

The majority of schizophrenia patients have cognitive deficits as a separate symptom cluster independent of positive or negative symptoms. Current medicines, unfortunately, cannot provide clear benefits for cognitive symptoms in patients. Recent findings showed decreased α7 nicotinic acetylcholine receptor (nAChR) expressions in subjects with schizophrenia. α7 nAChR full/partial agonists and positive allosteric modulators (PAMs) may be valuable drug candidates to treat cognitive deficits of disease. This study comparatively investigated the effect of α7 nAChR agonist (A-582941), type I PAM (CCMI), type II PAM (PNU-120596), and the antipsychotic drug (clozapine) on behavioral, molecular, and immunohistochemical parameters in a subchronic MK-801 model of schizophrenia in male rats. Novel object recognition (NOR) and Morris water maze (MWM) tests were performed to evaluate recognition and spatial memories, respectively. Gene and protein expressions of parvalbumin, glutamic acid decarboxylase-67 (GAD67), and α7 nAChR were examined in the rats' hippocampal tissue. The subchronic MK-801 administration produced cognitive deficits in the NOR and MWM tests. It also decreased the protein and gene expressions of parvalbumin, GAD67, and α7 nAChR in the hippocampus. Clozapine, A-582941, and PNU-120596 but not CCMI increased the parvalbumin and α7 nAChR expressions and provided benefits in recognition memory. Interestingly, clozapine and CCMI restored the MK-801 induced deficits on GAD1 expression and spatial memory while A-582941 and PNU-120596 were ineffective. These results indicated that α7 nAChR agonist, type I and type II PAMs may provide benefits in different types of cognitive deficits rather than a complete treatment in schizophrenia.

100 Deals associated with AVL-3288

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Central Nervous System Diseases	Preclinical	United States	University of California, Irvine	08 May 2007
Cognitive Dysfunction	Discovery	-	University of Maryland Baltimore	01 May 2018
Schizoaffective disorder	Discovery	United States	National Institute of Mental Health	01 Nov 2016
Schizophrenia	Discovery	United States	National Institute of Mental Health	01 Jun 2013
Cognition Disorders	Discovery	United States	Anvyl LLC	-
Cognition Disorders	Discovery	-	Anvyl Pharmaceuticals	-