RTI-31 ((–)-2β-carbomethoxy-3β-(4'-chlorophenyl)tropane) 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 ...

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

that acts as a

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

. Semi-synthesis of this compound is dependent upon the availability of cocaine starting material. According to the article, RTI-31 is 64 times the strength of cocaine in terms of its potency to elicit self-administration in monkeys. WIN 35428 was 6 times weaker than RTI-31, whereas

RTI-51 (–)-2β-Carbomethoxy-3β-(4-bromophenyl)tropane (RTI-''4229''-51, bromopane) is a semi-synthetic alkaloid in the phenyltropane group of psychostimulant compounds. First publicized in the 1990s, it has not been used enough to have gained a fully ...

was 2.6 times 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 RTI-336, also known as RTI-4229-336 or LS-193,309 is a potent and selective dopamine reuptake inhibitor that was initially developed by the Research Triangle Institute, now known as RTI International. Pharmacology It is a phenyltropane deriv ...

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 synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...

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. It may be possible that the NE levels are raised, at least in part, through DAT blockade. RTI-31 lies somewhere in the middle of the table between troparil on one end and

RTI-55 RTI(-''4229'')-55, also called RTI-55 or iometopane, is a phenyltropane-based stimulant, 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 ...

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.

References

{{Dopaminergics Tropanes RTI compounds Dopamine reuptake inhibitors Sympathomimetic amines 4-Chlorophenyl compounds Methyl esters

Binding and uptake selectivity

See also

References