(S)-MK-26

(S)-MK-26 is an atypical dopamine reuptake inhibitor (DRI) that was derived from modafinil.^[1][2][3] It is closely related to two other modafinil analogues, (S,S)-CE-158 and (S)-CE-123.^[2][3]

(S)-MK-26

Clinical data
Drug class	Atypical dopamine reuptake inhibitor
Identifiers
CAS Number	2407547-18-4
Chemical and physical data
Formula	C17H13Cl2NOS2
Molar mass	382.32 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC=C(Cl)C=C1C([S@@](=O)CC1SC=NC=1)C1=CC(Cl)=CC=C1
InChI InChI=InChI=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 Key:WOJHQJWZRIRCQE-QHCPKHFHSA-N

(S)-MK-26 has markedly improved potency and selectivity as a blocker of the dopamine transporter (DAT) compared to modafinil (IC₅₀Tooltip half-maximal inhibitory concentration = 49 nM vs. 6,400 nΜ; 130-fold difference).^[3]

It has pro-motivational effects in animals and reverses tetrabenazine-induced motivational deficits and depression-like behavior.^[1][3] 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.^[2][3]

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.^[2][4][3] It was first described by 2022.^[3]

See also

• List of modafinil analogues and derivatives
• MRZ-9547
• PRX-14040