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.
|Chemical and physical data|
|Molar mass||378.894 g/mol g·mol−1|
|3D model (JSmol)|
"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
|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(RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9).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.
- Lindsey, K.P.; Wilcox, K.M.; Votaw, J.R.; Goodman, M.M.; Plisson, C.; Carroll, F.I.; Rice, K.C.; Howell, L.L. (2004). "Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: relationship to transporter occupancy determined by positron emission tomography neuroimaging" (PDF). Journal of Pharmacology and Experimental Therapeutics. 309 (3): 959–969. doi:10.1124/jpet.103.060293. PMID 14982963. Archived from the original (PDF) on 2010-06-11.
- Carroll, FI; Howard, JL; Howell, LL; Fox, BS; Kuhar, MJ (Mar 2006). "Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse". The AAPS Journal. 8 (1): E196–203. doi:10.1208/aapsj080124. PMC 2751440. PMID 16584128.
- Kimmel, HL; O'Connor, JA; Carroll, FI; Howell, LL (January 2007). "Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys". Pharmacol. Biochem. Behav. 86 (1): 45–54. doi:10.1016/j.pbb.2006.12.006. PMC 1850383. PMID 17258302.