RTI-177 show
(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-2-(3-phenyl-1,2-oxazol-5-yl)-8-azabicyclo[3.2.1]octane
CAS Number 171236-00-3 HCl: 170939-95-4 PubChem CID ChemSpider ChEMBL Formula C 23 H 23 Cl N 2 O Molar mass 378.90 g·mol−1 3D model (JSmol ) show
CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)Cl)C4=CC(=NO4)C5=CC=CC=C5
show
InChI=1S/C23H23ClN2O/c1-26-18-11-12-21(26)23(19(13-18)15-7-9-17(24)10-8-15)22-14-20(25-27-22)16-5-3-2-4-6-16/h2-10,14,18-19,21,23H,11-13H2,1H3/t18-,19+,21+,23-/m0/s1
Key:ZGCYMNJHHKQEGA-KPYOPSEVSA-N
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 .[1] 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.[2]
"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)."[3]
Update [ ]
Lower reinforcing strength of the phenyltropane cocaine analogs RTI-336 and RTI-177 compared to cocaine in nonhuman primates.
Comparison of six MAT inhibitors [ ]
RTI
X
R
[3 H]CFT
[3 H]Nisoxetine
[3 H]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.[citation needed ]
"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(RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9).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."[2]
Also the potency of the heterocyclic compounds is not as great as would be predicted based on in vitro test results.
References [ ]
^ Lindsey KP, Wilcox KM, Votaw JR, Goodman MM, Plisson C, Carroll FI, et al. (June 2004). "Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: relationship to transporter occupancy determined by positron emission tomography neuroimaging" (PDF) . The Journal of Pharmacology and Experimental Therapeutics . 309 (3): 959–69. doi :10.1124/jpet.103.060293 . PMID 14982963 . S2CID 39794215 . Archived from the original (PDF) on 2010-06-11.
^ Jump up to: a b Carroll FI, Howard JL, Howell LL, Fox BS, Kuhar MJ (March 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" . Pharmacology, Biochemistry, and Behavior . 86 (1): 45–54. doi :10.1016/j.pbb.2006.12.006 . PMC 1850383 . PMID 17258302 .
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show Phenyltropanes (classifications )
2-Carboxymethyl Esters (3,4-Disubstituted Phenyl)-tropanes
Dichloropane
RTI-112
RTI-353
Arylcarboxy Carboxyalkyl Acyl β,α Stereochemistry α,β Stereochemistry Heterocycles: 3-Substituted-isoxazol-5-yl Heterocycles: 3-Substituted-1,2,4-oxadiazole N-alkyl N-replaced (S,O,C) Irreversible Nortropanes (N-demethylated)