Behavioral effects of three synthetic tryptamine derivatives in rodents

Aims: New synthetic tryptamine derivatives have emerged in the underground market. They act on serotonin receptors mimicking the effects of hallucinogenic drugs such as DOM. The DEA has identified three tryptamine derivatives of concern, 5-MeO-DBT, 5-Cl-DMT, and 4-OH-MiPT. Methods: Swiss Webster mice were tested for locomotor activity. Discriminative stimulus effects were tested in male Sprague-Dawley rats trained to discriminate DOM (0.5 mg/kg, 30-min pretreatment) from vehicle (0.9% saline). Results: In the locomotor activity tests, DOM (ED 50 = 4.8 mg/kg) produced a 40–100-min depressant phase. 5-MeO-DBT (ID 50 = 16.5 mg/kg; ED 50 = 0.074 mg/kg) had a 50-min depressant phase and a 100-min stimulant phase. 5-Cl-DMT (ID 50 = 12.3 mg/kg; ED 50 = 6.1 mg/kg) produced a 20–40-min depressant phase and a 30-min stimulant phase. 4-OH-MiPT (ID 50 = 5.8 mg/kg; ED 50 = 0.6 mg/kg) had a 30–130-min depressant phase and a 50-minute stimulant phase. In the drug discrimination assay, 4-OH-MIPT (ED 50 = 0.77 mg/kg) was fully substituted, whereas 5-Cl-DMT partially substituted for the discriminative stimulus effects produced by DOM (ED 50 = 0.23 mg/kg). 5-MeO-DBT failed to substitute for the discriminative stimulus of DOM. 5-CL-DMT and 5-MeO-DBT decreased response rate. Conclusion: The locomotor depressant effects of the three synthetic tryptamine derivatives were similar to DOM, but not as potent. In the drug discrimination assay, only 4-OH-MIPT was substituted fully for DOM. These results support the possibility that 4-OH-MIPT has abuse liability similar to DOM, whereas 5-MeO-DBT and 5-Cl-DMT may not.