Decynium-22 is a

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

ic derivative of

quinoline Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is a colorless hygroscopic liquid with a strong odor. Aged samples, especially if exposed to light, become yellow and later brown. Quinoline is only sli ...

, and a potent inhibitor of the plasma membrane monoamine transporter (PMAT), as well as all members of the organic cation transporter (OCT) family in both human and rat cells. However, it has little effect on high affinity

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ar ...

transporters such as the

dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...

and norepinephrine transporter.

Transporter inhibition

Decynium has been shown to have a very high affinity to organic cation transporters in a variety of species, including human, rat, and pig. Decynium-22 has been shown to block the uptake of the neurotoxin

1-methyl-4-phenylpyridinium MPP+ (1-methyl-4-phenylpyridinium) is a positively charged organic molecule with the chemical formula C12H12N+. It is a neurotoxin that acts by interfering with oxidative phosphorylation in mitochondria by inhibiting complex I, leading to the de ...

(MPP) via the OCT3 transporter in rat

astrocytes Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of ...

Fluorescence

Decynium-22 emits a low

fluorescence Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...

yield (around 0.001), and in its monomeric form is a weakly fluorescent. However, aggregated decynium-22 emits a strong superradiant emission with a maximum near 570–580 nm.Struganova IA. Dynamics of formation of 1,1′-diethyl-2,2′-cyanine iodide J-aggregates in solution. J Physical Chem A. 2000;104:9670–9674. 480 nm light falls near a short wavelength peak of the excitation spectrum of these aggregates. Decynium-22 fluorescence caused by aggregation can be observed in astrocytes.

Schizophrenia and depression

Decynium-22 has recently been investigated for its role in increasing

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

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 va ...

in the brain in neuropharmacology research. The transportation of the neurotransmitter serotonin is often disrupted in psychiatric disorders characterized by social impairment, such as

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

and depression. Serotonin is primarily taken up by the 5-HT transporter (SERT), although it is also taken up by auxiliary transporters, known as "uptake 2", which include OCT and PMAT. The most commonly prescribed antidepressant drugs are the

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

(SSRIs), which act by blocking the high affinity SERT. A proposed explanation for the limited efficacy of SSRIs is the presence of the low affinity transporters OCT and PMAT, which limit the ability of SSRIs to increase

serotonin. Decynium-22 blocked serotonin uptake via these auxiliary transporters, and when used in conjunction with SSRIs, decynium-22 enhanced the effects of SSRIs to inhibit serotonin clearance. A similar effect was seen in SERT

knock-out mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important ...

, which resulted in an improvement of social behavior. When OCT3 was knocked out in mice, however, decynium-22 was ineffectual, indicating that the anti-depressant effects of decynium-22 are dependent upon its blockage of the OCT3.

References

{{Adenosinergics Cations Enzyme inhibitors Adenosine reuptake inhibitors