RTI-112
Encyclopedia
RTI-112 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.
The in vitro tests actually show a very similar SERT
/DAT
/NET
selectivity to cocaine
, although in vivo they behave differently.
"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)."
The efficacy of cocaine analogs to elicit self administration is related to the rate at which they are administered.
Slower onset analogs are less likely to function as behavioral stimulants than analogs sporting a faster rate of onset.
Nonselective analogs are less likely to function as "reinforcers" than reuptake inhibitors that have DAT specificity.
In order for a DRI such as cocaine to induce euphoria PET scans on primates reveal that the DAT occupancy needs to be >60%.
RTI-112 is a particularly interesting nonselective cocaine-analog that has equipotent in vitro affinity at the SERT, NET and DAT, respectively.
RTI-112 was not reliably self-administered, in contrast to the DAT selective reuptake inhibitors that were used in this study.
Particularly notable is the fact that in vivo at the ED50, RTI-112 had no DAT occupancy at all.
At the ED50, (mostly) all of the RTI-112 occupied the SERT at this dose.
Significantly higher dose was required to get >70% DAT occupancy in the case of RTI-112.
However RTI-112 was still able to suppress cocaine administration at the ED50 suggesting a serotonergic mechanism was responsible for this.
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
drug from the phenyltropane
Phenyltropane
Phenyltropanes 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, they are not the only researchers that have prepared these...
family. In contrast to RTI-113
RTI-113
RTI-113 is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor . It has been suggested as a possible substitute drug for the treatment of cocaine addiction...
which is DAT selective, RTI-112 is a nonselective triple reuptake inhibitor.
The in vitro tests actually show a very similar SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
/DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
/NET
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
selectivity to cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, although in vivo they behave differently.
"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
RTI-171
-2β--3β-tropane is a phenyltropane derivative which acts as a selective dopamine reuptake inhibitor, with a relatively slow onset of action and short duration of effects found in animal studies....
and RTI-177
RTI-177
RTI-177 is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT...
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)."
The efficacy of cocaine analogs to elicit self administration is related to the rate at which they are administered.
Slower onset analogs are less likely to function as behavioral stimulants than analogs sporting a faster rate of onset.
Nonselective analogs are less likely to function as "reinforcers" than reuptake inhibitors that have DAT specificity.
In order for a DRI such as cocaine to induce euphoria PET scans on primates reveal that the DAT occupancy needs to be >60%.
RTI-112 is a particularly interesting nonselective cocaine-analog that has equipotent in vitro affinity at the SERT, NET and DAT, respectively.
RTI-112 was not reliably self-administered, in contrast to the DAT selective reuptake inhibitors that were used in this study.
Particularly notable is the fact that in vivo at the ED50, RTI-112 had no DAT occupancy at all.
At the ED50, (mostly) all of the RTI-112 occupied the SERT at this dose.
Significantly higher dose was required to get >70% DAT occupancy in the case of RTI-112.
However RTI-112 was still able to suppress cocaine administration at the ED50 suggesting a serotonergic mechanism was responsible for this.