RTI-177

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RTI(-4229)-177 (2β-(3-phenylisoxazol-5-yl)-3β-(4-chlorophenyl)tropane, β-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 (30–60 min) and a longer duration of action (10h). The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset (30–120 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)."

Comparison of six MAT inhibitors

RTI	X	R	[3H]CFT	[3H]Nisoxetine	[3H]Paroxetine
Coc	—	—	89.1	3298 (1986)	1045 (45)
177	Cl	phenyl	1.28	504 (304)	2420 (220)
176	Me	phenyl	1.58	398 (239)	5110 (465)
354	Me	ethyl	1.62	299 (180)	6400 (582)
336	Cl	*p*-cresyl	4.09	1714 (1033)	5741 (522)
386	Me	*p*-anisoyl	3.93	756 (450)	4027 (380)

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, 3β-(4-chlorophenyl)-2β-[3-(4’-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(RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9).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.