RTI(-4229)-177 (2ò-(3-phenylisoxazol-5-yl)-3ò-(4-chlorophenyl)tropane, ò-CPPIT) is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT. RTI-177 has an unusually long duration of action of 20 hours or more, substantially longer than the related compound RTI-336 from which it differs in molecular structure only by the absence of a p-methyl group.
"the nonselective monoamine transporter inhibitor RTI-126 and the DAT-selective inhibitors RTI-150 and RTI-336 both had a faster rate of onset (30 min) and a short duration of action (4h). In contrast, the nonselective monoamine transporter inhibitor RTI-112 had a slower rate of onset (30âÂÂ60 min) and a longer duration of action (10h). The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset (30âÂÂ120 min), but RTI-171 had a short duration of action (2.5 h) while RTI-177 had a very long duration of action (20 h)."
In the Lindsey paper, RTI-177 was wrongly considered to be a dual inhibitor of the NET, although this was later found out to be incorrect.
"In acute toxicity studies in male rats, 3ò-(4-chlorophenyl)-2ò-[3-(4âÂÂ-methylphenyl)isoxazol-5-yl]tropane (RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9). These results suggested that RTI-336 was a better candidate than RTI-177 for further preclinical development."
Also the potency of the heterocyclic compounds is not as great as would be predicted based on in vitro test results.