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 convent ...
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 sl ...
, and a potent inhibitor of the
plasma membrane monoamine transporter
The plasma membrane monoamine transporter (PMAT) is a low-affinity monoamine transporter protein which in humans is encoded by the ''SLC29A4'' gene. It is known alternatively as the human equilibrative nucleoside transporter-4 (hENT4). It was disc ...
(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 are ...
transporters such as the
dopamine transporter
The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...
and
norepinephrine transporter
The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene.
NET is a monoamine transporter and is responsible for the sodium ...
.
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 monoaminergic neurotoxin that acts by interfering with oxidative phosphorylation in mitochondria by inhibiting complex I, le ...
(MPP) via the
OCT3 transporter in rat
astrocytes
Astrocytes (from Ancient Greek , , "star" and , , "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 end ...
.
Fluorescence
Decynium-22 emits a low
fluorescence
Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with colore ...
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 (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
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 variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
and
depression. Serotonin is primarily taken up by the
5-HT transporter
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
(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 primarily work by blo ...
(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
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. 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 "Gene knockout, knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They ...
, 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