(–)-2β-Carbomethoxy-3β-(4'-chlorophenyl)tropane (RTI-''4229''-31) is a synthetic
analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
of
cocaine
Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...
that acts as a
stimulant.
Semi-synthesis of this compound is dependent upon the availability of cocaine starting material. According to the article,
[ RTI-31 is 64 x the strength of cocaine in terms of its potency to elicit self-administration in monkeys. WIN 35428 was 6 x weaker than RTI-31, whereas RTI-51 was 2.6 x weaker than RTI-31.
A further advantage, in addition to potency of this compound, is that its duration of activity is longer than for cocaine. It could therefore be considered within the context as an agonist based therapy for treating cocaine addiction, although it is actually RTI-336 that entered into clinical trials with this in mind. RTI-31 is already completely psychoactive in its own right meaning that further chemical manipulation should be viewed as an option that is not strictly necessary. RTI-336 is actually made using RTI-31 as starting material. RTI-31 is not an entirely selective DRI in that it also has appreciable SERT and NET blocking affinity. RTI-31 can easily be "cleaned" though, as is done, for instance, by replacing the carbomethoxy ester with a more sterically occluded substituent such as is done for RTI-113.
]
Binding and uptake selectivity
Based on the uptake of tritiated biogenic monoamine radiotracer
A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
s it can be confirmed by observing the figures in the attached table that RTI-31 is a relatively balanced reuptake inhibitor wrt the D/N/S ratio.
The binding ligand affinities for the different transporters is skewed somewhat in favor of the DAT; there may be some bias in the data. The reason for this could be that WIN35428 is relatively easier to displace from the DAT versus paroxetine from the SERT, because of the higher binding constant
The binding constant, or affinity constant/association constant, is a special case of the equilibrium constant ''K'', and is the inverse of the dissociation constant. It is associated with the binding and unbinding reaction of receptor (R) and li ...
of the former compound.
Also it needs to be borne in mind the idea of transporter promiscuity.RTI-55
RTI(-''4229'')-55, also called RTI-55 or iometopane, is a phenyltropane-based psychostimulant used in scientific research and in some medical applications. This drug was first cited in 1991. RTI-55 is a non-selective dopamine reuptake inhibitor d ...
on the other. It is not as selective as RTI-113 for the DAT, but is more selective than Dichloropane is for this transporter. RTI-31 also has some muscarinic acetylcholine agonist activity.
Data in Above table from rats brains (1995). More recent work has advocated using cloned human transporters.
See also
* (+)-CPCA
* RTI-336
* RTI-113
References
{{Dopaminergics
Tropanes
RTI compounds
Dopamine reuptake inhibitors
Sympathomimetic amines
Chlorobenzenes