This article may be too technical for most readers to understand.(August 2009) |
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ChemSpider | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
Chemical and physical data | |
Formula | C17H22ClNO2 |
Molar mass | 307.82 g·mol−1 |
3D model ( JSmol) | |
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(what is this?) (verify) |
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. [1]
In vitro tests show a very similar serotonin transporter (SERT)/ dopamine transporter (DAT)/ norepinephrine transporter (NET) selectivity to cocaine, [2] although in vivo behaviour is different:
"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]
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 a dopamine 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]
This article may be too technical for most readers to understand.(August 2009) |
Identifiers | |
---|---|
| |
CAS Number |
|
PubChem CID | |
ChemSpider | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
Chemical and physical data | |
Formula | C17H22ClNO2 |
Molar mass | 307.82 g·mol−1 |
3D model ( JSmol) | |
| |
| |
(what is this?) (verify) |
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. [1]
In vitro tests show a very similar serotonin transporter (SERT)/ dopamine transporter (DAT)/ norepinephrine transporter (NET) selectivity to cocaine, [2] although in vivo behaviour is different:
"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]
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 a dopamine 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]