Development of novel antipsychotic agents by inhibiting dopamine transporter – in silico approach

New Journal of Chemistry ◽

10.1039/d1nj04759k ◽

2022 ◽

Author(s):

Vladimir Đorđević ◽

Srđan Pešić ◽

Jelena Vladeta Zivkovic ◽

Goran M Nikolić ◽

Aleksandar M Veselinović

Keyword(s):

Dopamine Transporter ◽

In Silico ◽

Treatment Approach ◽

Antipsychotic Agents ◽

Research Paper ◽

Qsar Modeling ◽

Novel Antipsychotic

Dopamine transporter inhibition is deemed a promising schizophrenia treatment approach. This research paper outlines various QSAR modeling for molecules acting as dopamine transporter inhibitors. The SMILES notation and the local...

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Development of Potential Therapeutics for Pain Treatment by Inducing the Sigma 1 receptor Antagonism – In silico Approach

New Journal of Chemistry ◽

10.1039/d1nj00883h ◽

2021 ◽

Author(s):

Velimir Perić ◽

Mladjan Golubović ◽

Milan Lazarević ◽

Vesna Marjanović ◽

Tomislav Kostić ◽

...

Keyword(s):

In Silico ◽

Pain Treatment ◽

Treatment Approach ◽

Research Paper ◽

Qsar Modeling ◽

Receptor Antagonism ◽

Sigma 1 Receptor ◽

Sigma 1 ◽

Potential Therapeutics

The sigma 1 receptor antagonism is deemed a promising pain treatment approach. The research paper outlines conformational-independent QSAR modeling for a range of compounds which serve as sigma 1 receptor...

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Chemoinformatic studies on some inhibitors of dopamine transporter and the receptor targeting schizophrenia for developing novel antipsychotic agents

Heliyon ◽

10.1016/j.heliyon.2020.e04464 ◽

2020 ◽

Vol 6 (7) ◽

pp. e04464

Author(s):

Sabitu Babatunde Olasupo ◽

Adamu Uzairu ◽

Gideon Adamu Shallangwa ◽

Sani Uba

Keyword(s):

Dopamine Transporter ◽

Antipsychotic Agents ◽

Receptor Targeting ◽

Novel Antipsychotic

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Psychomotor stimulant effects of α-pyrrolidinovalerophenone (αPVP) enantiomers correlate with drug binding kinetics at the dopamine transporter

10.21203/rs.3.rs-612345/v1 ◽

2021 ◽

Author(s):

Marco Niello ◽

Spyridon Sideromenos ◽

Ralph Gradisch ◽

Ronan O'Shea ◽

Jakob Schwazer ◽

...

Keyword(s):

Dopamine Transporter ◽

In Silico ◽

Drug Binding ◽

Binding Kinetics ◽

Irreversible Binding ◽

Fast Kinetics ◽

Slow Dissociation ◽

Kinetics Of

Abstract α-Pyrrolidinovalerophenone (αPVP) is a psychostimulant and drug of abuse associated with severe intoxications in humans. αPVP exerts long-lasting psychostimulant effects, when compared to the classical dopamine transporter (DAT) inhibitor cocaine. Here, we compared the two enantiomeric forms of αPVP, the R- and the S-αPVP, with cocaine using a combination of in silico, in vitro and in vivo approaches. We found that αPVP enantiomers substantially differ from cocaine in their binding kinetics. The two enantiomers differ from each other in their association rates. However, they show similar slow dissociation rates leading to pseudo-irreversible binding kinetics at DAT. The pseudo-irreversible binding kinetics of αPVP is responsible for the observed non-competitive pharmacology and it correlates with persistent psychostimulant effects in mice. Thus, the slow binding kinetics of αPVP enantiomers profoundly differ from the fast kinetics of cocaine both in vitro and in vivo, suggesting drug-binding kinetics as a potential driver of psychostimulant effects in vivo.

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