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

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

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. Although RTI holds a strong position in this field, ...

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(-''4229'')-336, (LS-193,309, (−)-2β-(3-(4-methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane) is a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug. It binds to the dopamine ...

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

monoamine transporter Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible fo ...

inhibitor

RTI-126 RTI-126 (RTI-''4229''-126 or (–)-2β-(1,2,4-oxadiazol-5-methyl)-3β-phenyltropane) is a phenyltropane derivative which acts as a potent monoamine reuptake inhibitor and stimulant drug, and has been sold as a designer drug. It is around 5 times ...

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 fo ...

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 (–)-2β-(3-Methylisoxazol-5-yl)-3β-(p- tolyl)tropane (RTI-''4229''-171) is a phenyltropane derivative which acts as a selective dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhib ...

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, although this was later found out to be incorrect. "In acute toxicity studies in male rats, 3β-(4-chlorophenyl)-2β- -(4’-methylphenyl)isoxazol-5-ylropane (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 chemistry is the branch of organic chemistry dealing with the synthesis, properties, an ...

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

References

{{Phenyltropanes Chloroarenes Tropanes RTI compounds Dopamine reuptake inhibitors Stimulants Isoxazoles