RTI-336
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.
Pharmacology
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.Affinity of RIT-336 and analogs for the main monoamine transporters :
| RTI | X | R | CFT | Nisoxetine | Paroxetine | N ÷ D | S ÷ D |
| Coc | — | — | 89.1 | 3298 | 1045 | 37.01 | 11.79 |
| 177 | Cl | phenyl | 1.28 | 504 | 2420 | 393.8 | 1891 |
| 176 | Me | phenyl | 1.58 | 398 | 5110 | 251.9 | 3234 |
| 354 | Me | ethyl | 1.62 | 299 | 6400 | 184.6 | 3951 |
| 336 | Cl | p-tolyl | 4.09 | 1714 | 5741 | 419.1 | 1404 |
| 386 | Me | p-anisyl | 3.93 | 756 | 4027 | 192.4 | 1025 |
- CFT: CFT is a selective radioligand for the dopamine transporter
- Nisoxetine: This is a radioligand for the norepinephrine transporter
- Paroxetine: This is a radioligand for the serotonin transporter
- N ÷ D: ratio of norepinephrine transporter affinity to dopamine transporter affinity
- S ÷ D: ratio of serotonin transporter affinity to dopamine transporter affinity
Animal studies
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.