RTI-336, also known as RTI-4229-336 or LS-193,309 is a potent and selective dopamine reuptake inhibitor that was initially developed by the Research Triangle Institute, now known as RTI International.
It is a phenyltropane derivative that binds to the dopamine transporter with approximately 20 times the affinity of cocaine. However, it produces relatively mild stimulant effects, with a slow onset and a long duration of action. (Although, other sources classify it as having among the faster onsets of action among phenyltropanes.)
Affinity of RIT-336 and analogs for the main monoamine transporters (DAT, NET, SERT):
These characteristics make it a potential candidate for the treatment of cocaine addiction, as a possible substitute drug, analogous to the use of methadone for treating heroin dependence. RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration, and significantly reduces rates of cocaine use, especially when combined with SSRIs. Research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
RTI-336 and RTI-177 exhibited lower reinforcing strength than cocaine in nonhuman primates, indicating reduced abuse liability and supporting their viability as pharmacotherapies for addiction.
Chronic RTI-336 administration in rhesus monkeys altered motor activity and sleep patterns but did not cause adverse hormonal changes, suggesting a relatively safe profile for long-term therapeutic use.
A dosage of up to 20mg has been tolerated in healthy males.