RTI(-''4229'')-177 (2β-(3-phenylisoxazol-5-yl)-3β-(4-chlorophenyl)tropane, β-CPPIT) is a synthetic

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

drug from the

phenyltropane Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. This research has spanned beyond the last couple decade ...

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 RTI-336, also known as RTI-4229-336 or LS-193,309 is a potent and selective dopamine reuptake inhibitor that was initially developed by the Research Triangle Institute, now known as RTI International. Pharmacology It is a phenyltropane deriv ...

from which it differs in molecular structure only by the absence of a ''p''-methyl group. "the nonselective

monoamine transporter Monoamine transporters (MATs) are proteins that function as integral Cell membrane, plasma-membrane Neurotransmitter transporter, transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are se ...

inhibitor RTI-126 and the DAT-selective inhibitors

RTI-150 RTI(-''4229'')-150, ((−)-2β-Carbocyclobutoxy-3β-(4-methylphenyl)tropane) is a phenyltropane derivative which acts as a potent dopamine reuptake inhibitor and stimulant drug. It is around 5x more potent than cocaine, but is more selective for ...

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 RTI(-''4229'')-112 (2β-carbomethoxy-3β-(3-methyl-4-chlorophenyl)tropane) is a synthetic stimulant drug from the phenyltropane family. In contrast to RTI-113, which is DAT selective, RTI-112 is a nonselective triple reuptake inhibitor. ''In ...

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)."

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

In the Lindsey paper, RTI-177 was wrongly considered to be a dual inhibitor of the

NET NET may refer to: Broadcast media United States * National Educational Television, the predecessor of the Public Broadcasting Service (PBS) in the United States * National Empowerment Television, a politically conservative cable TV network ...

, although this was later found out to be incorrect. "In acute toxicity studies in male rats, 3β-(4-chlorophenyl)-2β-

-(4’-methylphenyl)isoxazol-5-yl The symbol , known in Unicode as hyphen-minus, is the form of hyphen most commonly used in digital documents. On most keyboards, it is the only character that resembles a minus sign or a dash, so it is also used for these. The name ''hyphen-min ...

ropane (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 compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

s is not as great as would be predicted based on ''in vitro'' test results.

References

{{Phenyltropanes 4-Chlorophenyl compounds Tropanes RTI compounds Dopamine reuptake inhibitors Stimulants Isoxazoles Phenyl compounds