JJC8-088 is a dopamine reuptake inhibitor (DRI) that was derived from the wakefulness-promoting agent modafinil.
It has substantially higher affinity for the dopamine transporter (DAT) than modafinil (K<sub>i</sub> = 6.72nM vs. 2,600nM; 387-fold). In contrast to modafinil and other analogues, which are atypical DRIs, JJC8-088 is a typical cocaine-like DRI. It has potent cocaine-like psychostimulant effects, produces robust and dose-dependent increases in dopamine levels in the nucleus accumbens, and is readily self-administered by and substitutes for cocaine in animals.
Similarly to cocaine, but unlike modafinil and other analogues, JJC8-088 stabilizes the DAT in an outward-facing open conformation. It has been theorized that cocaine-like DRIs may actually act as dopamine releasing agent-like DAT "inverse agonists" rather than as simple transporter blockers.
In addition to its affinity for the DAT, JJC8-088 has low affinity for the serotonin transporter (SERT) (K<sub>i</sub> = 213nM; 32-fold less than for the DAT) and for the norepinephrine transporter (NET) (K<sub>i</sub> = 1950nM; 290-fold less than for the DAT). It also binds with high affinity to the sigma ÃÂ<sub>1</sub> receptor (K<sub>i</sub> = 41.6nM).
The drug has high affinity for the hERG antitarget ( = 130nM) and could produce cardiotoxicity, which might cause a risk of heart attack if JJC8-088 were to be used recreationally.