Delving into the Latest Updates on Etazolate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Etazolate hydrochloride (USAN)

+ [2]

Target

GABAA receptor x PDE4

Mechanism

GABAA receptor modulators(Gamma-aminobutyric acid A receptor modulators), PDE4 inhibitors(Phosphodieterase 4 inhibitors), α-secretases stimulants(Alpha secretases stimulants)

Therapeutic Areas

Nervous System DiseasesOther DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication-

Inactive Indication

Alzheimer DiseaseCognition DisordersDementia, Vascular+ [2]

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

Exonhit

Bristol Myers Squibb Co.Eurobio-Scientific SA

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC14H19N5O2

InChIKeyOPQRBXUBWHDHPQ-UHFFFAOYSA-N

CAS Registry51022-77-6

A Pilot, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase IIA Study to Determine the Clinical Safety/Tolerability and Exploratory Efficacy of EHT 0202 (40 and 80 mg Bid) as Adjunctive Therapy to Acetylcholinesterase Inhibitor Over a 3-month Period in Ambulatory Patients Suffering From Mild to Moderate Alzheimer's Disease (EHT 0202/002 Protocol)

The objective of this 3-month study is to assess the safety and efficacy of EHT 0202 in addition to acetylcholinesterase inhibitor in patients suffering from Alzheimer's Disease.

Start Date01 Apr 2008

Sponsor / Collaborator

Exonhit

EUCTR2007-005549-39-FR / Unknown statusNot Applicable

A pilot, randomized, double-blind, placebo-controlled, parallel group, multicentre, phase IIa study to determine the clinical safety/tolerability and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to acetylcholinesterase inhibitor over a 3-month period in ambulatory patients suffering from mild to moderate Alzheimer’s Disease (EHT 0202/002 protocol).

Start Date19 Dec 2007

Sponsor / Collaborator

Exonhit

100 Clinical Results associated with Etazolate

Login to view more data

100 Translational Medicine associated with Etazolate

Login to view more data

100 Patents (Medical) associated with Etazolate

Login to view more data

68

Literatures (Medical) associated with Etazolate

27 May 2022·Journal of Natural ProductsQ2 · BIOLOGY

Clerodane Diterpenes from Casearia corymbosa as Allosteric GABA_A Receptor Modulators

Q2 · BIOLOGY

Review

Author: Hamburger, Matthias ; Garifulina, Aleksandra ; Danton, Ombeline ; Gupta, Mahabir P. ; Hering, Steffen ; Syafni, Nova ; Faleschini, Maria Teresa

An EtOAc extract of Casearia corymbosa leaves led to an allosteric potentiation of the GABA signal in a fluorometric imaging plate reader (FLIPR) assay on Chinese hamster ovary (CHO) cells stably expressing GABA_A receptors with an α₁β₂γ₂ subunit composition. The activity was tracked by HPLC-based activity profiling, and four known (2, 3, 4, and 8) and five new clerodane-type diterpenoids (1, 5-7, and 9) were isolated. Compounds 1-8 were obtained from the active time window. The absolute configuration of all compounds was established by ECD. Compounds 3, 7, and 8 exhibited EC₅₀ values of 0.5, 4.6, and 1.4 μM, respectively. To explore possible binding sites at the receptor, the most abundant diterpenoid 8 was tested in combination with diazepam, etazolate, and allopregnanolone. An additive potentiation of the GABA signal was observed with these compounds, while the effect of 8 was not inhibited by flumazenil, a negative allosteric modulator at the benzodiazepine binding site. Finally, the activity was validated in voltage clamp studies on Xenopus laevis oocytes transiently expressing GABA_A receptors of the α₁β₂γ₂S and α₁β₂ subtypes. Compound 8 potentiated GABA-induced currents with both receptor subunit compositions [EC₅₀ (α₁β₂γ₂S) = 43.6 μM; E_max = 809% and EC₅₀ (α₁β₂) = 57.6 μM; E_max = 534%]. The positive modulation of GABA-induced currents was not inhibited by flumazenil, thereby confirming an allosteric modulation independent of the benzodiazepine binding site.

01 Mar 2022·NeuropharmacologyQ2 · MEDICINE

Antiallodynic action of phosphodiesterase inhibitors in a mouse model of peripheral nerve injury

Q2 · MEDICINE

Article

Author: Bohren, Yohann ; Bourguignon, Jean-Jacques ; Freund-Mercier, Marie-José ; Megat, Salim ; Schlichter, Remy ; Journée, Sarah H ; Lacaud, Adrien ; Yalcin, Ipek ; Lelièvre, Vincent ; Villa, Pascal ; Hugel, Sylvain ; Barrot, Michel ; Doridot, Stéphane ; Salvat, Eric

Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory nervous system. It is accompanied by neuronal and non-neuronal alterations, including alterations in intracellular second messenger pathways. Cellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) are regulated by phosphodiesterase (PDE) enzymes. Here, we studied the impact of PDE inhibitors (PDEi) in a mouse model of peripheral nerve injury induced by placing a cuff around the main branch of the sciatic nerve. Mechanical hypersensitivity, evaluated using von Frey filaments, was relieved by sustained treatment with the non-selective PDEi theophylline and ibudilast (AV-411), with PDE4i rolipram, etazolate and YM-976, and with PDE5i sildenafil, zaprinast and MY-5445, but not by treatments with PDE1i vinpocetine, PDE2i EHNA or PDE3i milrinone. Using pharmacological and knock-out approaches, we show a preferential implication of delta opioid receptors in the action of the PDE4i rolipram and of both mu and delta opioid receptors in the action of the PDE5i sildenafil. Calcium imaging highlighted a preferential action of rolipram on dorsal root ganglia non-neuronal cells, through PDE4B and PDE4D inhibition. Rolipram had anti-neuroimmune action, as shown by its impact on levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) in the dorsal root ganglia of mice with peripheral nerve injury, as well as in human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides. This study suggests that PDEs, especially PDE4 and 5, may be targets of interest in the treatment of neuropathic pain.

01 Feb 2021·NeuroscienceQ3 · MEDICINE

Effect of Etazolate upon Cuprizone-induced Demyelination In Vivo: Behavioral and Myelin Gene Analysis

Q3 · MEDICINE

Article

Author: Meffre, Delphine ; Padilla-Ferrer, Aïda ; Carrete, Alex ; Jafarian-Tehrani, Mehrnaz ; Simon, Anne

Demyelination is a well-known pathological process in CNS disorders such as multiple sclerosis (MS). It provokes progressive axonal degeneration and functional impairments and no efficient therapy is presently available to combat such insults. Recently, we have shown that etazolate, a pyrazolopyridine compound and an α-secretase activator, was able to promote myelin protection and remyelination after cuprizone (CPZ)-induced acute demyelination in C57Bl/6 mice. In continuation of this work, here we have further investigated the effects of etazolate treatment after acute cuprizone-induced demyelination at the molecular level (expression of myelin genes Plp, Mbp and Mag and inflammatory markers Il-1β, Tnf-α) and at the functional level (locomotor and spatial memory skills) in vivo. To this end, we have employed two protocols which consists of administering etazolate (10 mg/kg/d) for a period of 2 weeks either during (Protocol #1) or after (Protocol #2) 5-weeks of CPZ-induced demyelination. At the molecular level, we observed that CPZ intoxication altered inflammatory and myelin gene expression and it was not restored with either of the etazolate treatment protocols. At the functional level, the locomotor activity was impaired after 3-weeks of CPZ intoxication (Protocol #1) and our data indicates a modest but beneficial effect of etazolate treatment. Spatial memory evaluated was not affected either by CPZ intake or etazolate treatment in both protocols. Altogether, this study shows that the beneficial effect of etazolate upon demyelination does not occur at the gene expression level at the time points studied. Furthermore, our results also highlight the difficulty in revealing functional sequelae following CPZ intoxication.

100 Deals associated with Etazolate

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D02655	Etazolate	-	-

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	FR	Exonhit	01 Apr 2008
Cognition Disorders	Phase 2	-	Bristol Myers Squibb Co.	-
Cognition Disorders	Phase 2	-	Eurobio-Scientific SA	-
Dementia, Vascular	Phase 2	FR	Exonhit	-
Parkinson Disease	Phase 2	FR	Exonhit	-
Retinal Diseases	Phase 2	FR	Exonhit	-