The novel atypical dopamine transport inhibitor CT-005404 has pro-motivational effects in neurochemical and inflammatory models of effort-based dysfunctions related to psychopathology

Q2 · MEDICINE

Article

Author: Asar, Sokaina ; Correa, Merce ; Yang, Jen-Hau ; Presby, Rose E ; Tracy, Olivia ; Murray, Fraser ; Salamone, John D ; Rotolo, Renee A

Depressed individuals suffer from effort-related motivational symptoms such as anergia and fatigue, which are resistant to treatment with many common antidepressants. While drugs that block dopamine transport (DAT) reportedly have positive motivational effects, DAT inhibitors such as cocaine and amphetamines produce undesirable side effects. Thus, there is a need to develop and characterize novel atypical DAT inhibitors with unique and selective binding profiles. Rodent effort-based choice tasks provide useful models of motivational dysfunctions. With these tasks, animals choose between a high-effort instrumental action leading to highly valued reinforcement vs. a low effort/low reward option. The present studies focused on the initial characterization of a novel atypical DAT inhibitor, CT-005404, which binds to DAT with high selectivity relative to serotonin and norepinephrine transport, and produces long-term elevations of extracellular DA. CT-005404 was assessed for its ability to attenuate the effort-related motivational effects of the DA depleting agent tetrabenazine and the pro-inflammatory cytokine interleukin-1β (IL-1β) using a fixed ratio 5/chow feeding choice test. Tetrabenazine (1.0 mg/kg i.p.) shifted choice behavior, decreasing lever pressing and increasing chow intake. IL-1β (4.0 μg/kg i.p.) also decreased lever pressing. CT-005404 was co-administered (7.5-30.0 mg/kg p.o.) with either tetrabenazine or IL-1β, and the 15.0 and 30.0 mg/kg doses significantly reversed the effects of tetrabenazine and IL-1β. CT-005404 administered alone produced a dose-related increase in lever pressing in rats tested on a progressive ratio/chow feeding choice task. Atypical DAT inhibitors such as CT-005404 offer potential as a new avenue for drug treatment of motivational dysfunctions in humans.

100 Deals associated with CTDP-001

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Fatigue	Preclinical	-	Chronos Therapeutics Ltd.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

CTDP-001

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation