 | This articlemay be too technical for most readers to understand. Pleasehelp improve it tomake it understandable to non-experts, without removing the technical details.(August 2009) (Learn how and when to remove this message) |
 | |
| Identifiers | |
|---|---|
| |
| CAS Number |
|
| PubChemCID | |
| ChemSpider |
|
| UNII | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C17H22ClNO2 |
| Molar mass | 307.82 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
 N Y (what is this?) (verify) | |
RTI(-4229)-112 (2β-carbomethoxy-3β-(3-methyl-4-chlorophenyl)tropane) is a syntheticstimulant drug from thephenyltropane family. It is primarily used in scientific research to study the brain'sreward system. In contrast to more well-known stimulants that primarily affect one type of brain cell communication, RTI-112 is a nonselectivetriple reuptake inhibitor. This means it simultaneously affects three important brain chemicals:serotonin,dopamine, andnorepinephrine.[1]
In vitro tests show a very similarserotonin transporter (SERT)/dopamine transporter (DAT)/norepinephrine transporter (NET) selectivity tococaine,[2] although in vivo behaviour is different:
"Thenonselective monoamine transporter inhibitorRTI-126 and the DAT-selective inhibitorsRTI-150 andRTI-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 inhibitorsRTI-171 andRTI-177 also had slower rates of onset (30–120 min), but RTI-171 had a short duration of action (2.5 h) whileRTI-177 had a very long duration of action (20 h)."[3]
The efficacy of cocaine analogs to elicit self-administration is related to the rate at which they are administered.[clarification needed] Slower onset analogs are less likely to function as behavioral stimulants than analogs eliciting a faster rate of onset.[4] Nonselective analogs are less likely to function as "reinforcers" than reuptake inhibitors that have DAT specificity.[3]
In order for adopamine reuptake inhibitor (DRI) such as cocaine to induce euphoria,PET scans on primates reveal that the DAT occupancy needs to be >60%.[5]
RTI-112 has equipotent in vitro affinity at the SERT, NET and DAT, respectively.[2] RTI-112 was not reliably self-administered, in contrast to the DAT selective reuptake inhibitors that were used in this study.[2]
In vivo at the ED50, RTI-112 had no DAT occupancy at all.[2] At the ED50, almost all of the RTI-112 occupied the SERT at this dose.[2] A significantly higher dose was required to get >70% DAT occupancy in the case of RTI-112;[2] however, RTI-112 was still able to suppress cocaine administration at the ED50, suggesting a serotonergic mechanism was responsible for this.[2]
