(S)-MK-26

Atypical dopamine reuptake inhibitor S (S)-MK-26 (S)-MK-26.svg skin-invert-image Atypical dopamine reuptake inhibitor 2407547-18-4 17 13 2 1 1 2 C1=CC=C(Cl)C=C1C([S@@](=O)CC1SC=NC=1)C1=CC(Cl)=CC=C1 1S/C17H13Cl2NOS2/c18-14-5-1-3-12(7-14)17(13-4-2-6-15(19)8-13)23(21)10-16-9-20-11-22-16/h1-9,11,17H,10H2/t23-/m0/s1 WOJHQJWZRIRCQE-QHCPKHFHSA-N (S)-MK-26 is an atypical dopamine reuptake inhibitor (DRI) that was derived from modafinil. Salamone JD, Correa M The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine Annu Rev Psychol 75 1–32 January 2024 37788571 10.1146/annurev-psych-020223-012208 10234/207207 free Hersey M, Bartole MK, Jones CS, Newman AH, Tanda G Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors Molecules 28 13 July 2023 5270 37446929 10343811 10.3390/molecules28135270 free Kouhnavardi S, Ecevitoglu A, Dragačević V, Sanna F, Arias-Sandoval E, Kalaba P, Kirchhofer M, Lubec J, Niello M, Holy M, Zehl M, Pillwein M, Wackerlig J, Murau R, Mohrmann A, Beard KR, Sitte HH, Urban E, Sagheddu C, Pistis M, Plasenzotti R, Salamone JD, Langer T, Lubec G, Monje FJ A Novel and Selective Dopamine Transporter Inhibitor, (S)-MK-26, Promotes Hippocampal Synaptic Plasticity and Restores Effort-Related Motivational Dysfunctions Biomolecules 12 7 June 2022 881 35883437 9312958 10.3390/biom12070881 free It is closely related to two other modafinil analogues, (S,S)-CE-158 and (S)-CE-123. (S)-MK-26 has markedly improved potency and selectivity as a blocker of the dopamine transporter (DAT) compared to modafinil (IC50 half-maximal inhibitory concentration = 49nM vs. 6,400nΜ; 130-fold difference). It has pro-motivational effects in animals and reverses tetrabenazine-induced motivational deficits and depression-like behavior. The drug dose-dependently increases extracellular dopamine levels in the nucleus accumbens and prefrontal cortex, does not modify locomotor activity (a measure of psychostimulant-like effect), and slightly enhances spatial memory in animals. There has been interest in (S)-MK-26 as a potential treatment for depression, psychostimulant use disorder (PSUD), Alzheimer's disease, and aging-related disorders. Shaikh A, Ahmad F, Teoh SL, Kumar J, Yahaya MF Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease Front Cell Neurosci 17 1292858 2023 38026688 10679733 10.3389/fncel.2023.1292858 free It was first described by 2022. See also List of modafinil analogues and derivatives MRZ-9547 PRX-14040 References Category:3-Chlorophenyl compounds Category:Dopamine reuptake inhibitors Category:Experimental drugs Category:Pro-motivational agents Category:Sulfoxides Category:Thiazoles Category:Modafinil analogues