RTI-113
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| Formula | C21H22ClNO2 |
| Molar mass | 355.86 g·mol−1 |
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RTI(-4229)-113 (2β-carbophenoxy-3β-(4-chlorophenyl)tropane) is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor (DRI). It has been suggested as a possible substitute drug for the treatment of cocaine addiction. "RTI-113 has properties that make it an ideal medication for cocaine abusers, such as an equivalent efficacy, a higher potency, and a longer duration of action as compared to cocaine."[1] Replacing the methyl ester in RTI-31 with a phenyl ester makes the resultant RTI-113 fully DAT specific. RTI-113 is a particularly relevant phenyltropane cocaine analog that has been tested on squirrel monkeys.[2] RTI-113 has also been tested against cocaine in self-administration studies for DAT occupancy by PET on awake rhesus monkeys.[3] The efficacy of cocaine analogs to elicit self-administration is closely related to the rate at which they are administered.[4] Slower onset of action analogs are less likely to function as positive reinforcers than analogues that have a faster rate of onset.[4][5]
In order for a DRI such as cocaine to induce euphoria PET scans on primates reveal that the DAT occupancy needs to be >60%.[6] Limited reinforcement may be desirable because it can help with patient compliance. DAT occupancy was between 65 and 76% and 94-99% for doses of cocaine and RTI-113 that maintained maximum response rates, respectively.[3] Whereas cocaine is a fast acting rapidly metabolized DRI, RTI-113 has a longer duration span.[7]
Self-administration graphs are inverted U-shaped. More doses of cocaine need to be administered per session than for RTI-113 because cocaine doesn't last as long as RTI-113 does. It is easy to form the rash judgement that the NRI and SRI properties of cocaine are somehow having an additive effect on provoking self-administration of cocaine.[8]
Although NRIs are known to inhibit DA reuptake in the prefrontal cortex where DATs are low in number, the fact that desipramine is not reliably self-administered makes it unlikely that NRIs are contributing to the addictive character of cocaine.[9]
The 5-HT receptors are very complex to understand and can either mediate or inhibit DA release.
However, on the whole, it is understood that synaptic 5-HT counterbalances catecholamine release.
Thus, it can said with relative certainty that the DAT is responsible for the bulk of the reinforcing effects of cocaine and related stimulants.[10]
With regard to amphetamine, a recent paper disputes this claim, and makes the point that the role of NE is completely underrated.[11]
Another paper was also recently published, seeking to address the relevance of NE in cocaine pharmacology.[12]