RTI-83 ((–)-2β-carbomethoxy-3β-(4-ethylphenyl)tropane) is a

phenyltropane Phenyltropanes (PTs) 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, the ...

derivative which represents a rare example of an SDRI or serotonin-dopamine reuptake inhibitor, a drug which inhibits the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transm ...

of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

, while having little or no effect on the reuptake of the related neurotransmitter

noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

. With a

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mol ...

(K_i) of 55 nM at DAT and 28.4 nM at SERT but only 4030 nM at

NET Net or net may refer to: Mathematics and physics * Net (mathematics), a filter-like topological generalization of a sequence * Net, a linear system of divisors of dimension 2 * Net (polyhedron), an arrangement of polygons that can be folded up ...

, RTI-83 has reasonable selectivity for DAT/SERT over NET However, further research has shown that by extending the ethyl chain even better selectivity can be achieved, with the 4′-(''cis''-propenyl) analogue having K_i values of 15 nM at DAT and 7.1 nM at SERT, vs 2800 nM at NET. However RTI-436 has an even better selectivity for DAT over NET (3.09nM @ DAT & 1,960nM @ NET or a NET/DAT ratio of 634.3, but with lesser DAT/SERT equivalent potency with a ratio between them of 108) and RTI-88 has a still better ratio (984 NET/DAT with additionally having less selectivity than the former compound between DAT/SERT and having a more even spread of potency with the ratio between DAT & SERT being 88) Such drugs are speculated to be useful as potential

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s, but few examples have been reported in the literature as yet. However, while RTI-83 has been used for binding studies to model the

monoamine transporter Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible for ...

proteins, its pharmacology ''in vivo'' has not been studied in detail.

References

External links

* {{Dopaminergics Tropanes RTI compounds Serotonin–dopamine reuptake inhibitors Sympathomimetic amines

See also

References

External links