Delving into the Latest Updates on S-33138 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

D3 receptor

Mechanism

D3 receptor antagonists(Dopamine D3 receptor antagonists)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Schizophrenia

Originator Organization

Les Laboratoires Servier SAS

Active Organization-

Inactive Organization

Les Laboratoires Servier SAS

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H23N3O2

InChIKeyZDZWIQDJFWTDAM-GHTZIAJQSA-N

CAS Registry245514-32-3

INTRODUCTIONSchizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D₂ receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: The prospect of developing a dopamine antagonist is hopeful. Brexpiprazole and cariprazine, which were agents listed as 'investigational dopamine antagonists,' just received FDA approval. Novel agents such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available, and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation. However, the expected benefits of the newly developed antagonists may not be great because they offer little enhanced efficacy for negative symptoms, cognition and functional outcomes.

01 Dec 2012·Journal of NeurochemistryQ2 · MEDICINE

Pharmacological or genetic blockade of the dopamine D3 receptor increases cell proliferation in the hippocampus of adult mice

Q2 · MEDICINE

Article

Author: Millan, Mark J. ; Mocaer, Elisabeth ; Egeland, Martin ; Svenningsson, Per ; Zhang, Xiaoqun

AbstractDopamine plays an important role in cellular processes controlling the functional and structural plasticity of neurons, as well as their generation and proliferation, both in the developing and the adult brain. The precise roles of individual dopamine receptors subtypes in adult neurogenesis remain poorly defined, although D3 receptors are known to be involved in neurogenesis in the subventricular zone. By contrast, very few studies have addressed the influence of dopamine and D3 receptors upon neurogenesis in the subgranular zone of the hippocampus, an issue addressed herein employing constitutive D3 receptor knockout mice, or chronic exposure to the preferential D3 receptor antagonist, S33138. D3 receptor knockout mice revealed increased baseline levels of cell proliferation and ongoing neurogenesis, as measured both using Ki‐67 and doublecortin, whereas there was no difference in cell survival as measured by BrdU (5‐bromo‐2′‐deoxyuridine). Chronic administration of S33138 was shown to be functionally active in enhancing levels of the plasticity‐related molecule, delta‐FosB, in the D3 receptor‐rich nucleus accumbens. In accordance with the stimulated neurogenesis seen in D3 receptor knockout mice, S33138 increased proliferation in wild‐type mice. These observations suggest that D3 receptors exert a tonic, constitutive inhibitory influence upon adult hippocampal neurogenesis.

01 Nov 2012·SynapseQ4 · MEDICINE

The effects of the preferential dopamine D₃ receptor antagonist S33138 on ethanol binge drinking in C57BL/6J mice

Q4 · MEDICINE

Article

Author: Ashby, Charles R. ; Rice, Onarae V. ; Patrick, Jay ; Ning, Haoran ; Schonhar, Charles D.

AbstractThe mesolimbic dopamine (DA) pathway plays an integral role in the reinforcing properties of many drugs of abuse, including alcohol (ethanol/EtOH). It has been reported that selective and acute blockade of the DA D3 receptor by SB‐277011A will attenuate EtOH preference, intake, and lick responses in EtOH preferring rats. However, alcohol consumption that leads to abuse is often marked by binge drinking—which is characterized as bringing ones blood EtOH levels to ≥80 mg/dL within 2 hours of the initial drink. It is unclear if brain mechanisms implicated in EtOH reward are equally implicated in EtOH binge consumption and abuse. Therefore, in this study, we examined the effect of the preferential D3 receptor antagonist S33138 on ethanol (6% v/v) and water consumption in male C57BL/6J mice using a restricted‐access binge‐drinking model. Ethanol drinking was not significantly altered by the intraperitoneal (i.p.) administration of 0.16 mg/kg of S33138. In contrast, the i.p. administration of 0.64 or 2.5 mg/kg i.p. of S33138 produced a significant decrease in ethanol consumption on days 1 and 7 and days 7–14 compared to vehicle treated animals. However, the mean water consumption was significantly decreased by (1) 0.16 and 0.64 mg/kg i.p. of S33138 on Day 1 and (2) 2.5 mg/kg i.p. of S33138 at Days 1, 7, and 7–14. Our studies indicate that a low dose of S33138 significantly decreases binge drinking, and that it does not significantly alter the consumption of water. In addition, S33138 alone is not appetitive. Synapse 66:975–978, 2012. © 2012 Wiley Periodicals, Inc.

100 Deals associated with S-33138

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Phase 2	DE	Les Laboratoires Servier SAS	-
Schizophrenia	Phase 2	AT	Les Laboratoires Servier SAS	-
Schizophrenia	Phase 2	HU	Les Laboratoires Servier SAS	-