N-Acetylserotonin also known as normelatonin, is a naturally occurring

Natural product

A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...

 chemical

Chemical compound

A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...

 intermediate

Reaction intermediate

A reaction intermediate or an intermediate is a molecular entity that is formed from the reactants and reacts further to give the directly observed products of a chemical reaction. Most chemical reactions are stepwise, that is they take more than one elementary step to complete...

 in the endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 production of melatonin

Melatonin

Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...

 from serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

. It is produced from serotonin by the enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 aralkylamine N-acetyltransferase

Aralkylamine N-acetyltransferase

In enzymology, an aralkylamine N-acetyltransferase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are acetyl-CoA and 2-arylethylamine, whereas its two products are CoA and N-acetyl-2-arylethylamine....

 (AANAT) and is converted to melatonin by acetylserotonin O-methyltransferase

Acetylserotonin O-methyltransferase

N-Acetylserotonin O-methyltransferase also known as ASMT is an enzyme that catalyzes the final reaction in melatonin biosynthesis, converting Normelatonin to melatonin. This reaction is embedded in the more general tryptophan metabolism pathway...

 (ASMT). Like melatonin, NAS is an agonist

Agonist

An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

 at the melatonin receptor

Melatonin receptor

A melatonin receptor is a G protein-coupled receptor which binds melatonin.Three types of melatonin receptor have been cloned. The MT1 and MT2 receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT3 has been identified in amphibia and...

s MT₁, MT₂, and MT₃, and may be considered to be a neurotransmitter

Neurotransmitter

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

. In addition, NAS is distributed in some areas of the brain

Brain

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 where serotonin and melatonin are not, suggesting that it may have unique central duties of its own instead of merely functioning as a precursor in the synthesis of melatonin.

Recently, NAS has been shown to act as a potent

Potency (pharmacology)

In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 TrkB receptor agonist, while serotonin and melatonin are not. It produces robust antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

, neuroprotective, and neurotrophic effects that are TrkB-mediated. In addition, AANAT knockout mice

Knockout mouse

A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...

 which lack NAS display significantly greater immobility times versus control mice in assays of depression like the forced swim test.

NAS may also play a major role in the antidepressant effects of selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitor

Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

s (SSRIs) and monoamine oxidase inhibitor

Monoamine oxidase inhibitor

Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

s (MAOIs). The SSRI fluoxetine

Fluoxetine

Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...

 and the MAO-A inhibitor

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

 clorgyline

Clorgyline

Clorgyline is an irreversible and selective inhibitor of monoamine oxidase A that is used in scientific research. It is structurally related to pargyline.- References :...

 upregulate AANAT indirectly through serotonergic

Serotonergic

Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

 mechanisms and thereby increase NAS levels after chronic administration, and this correlates with the onset of their antidepressant effects. Furthermore, light exposure inhibits the synthesis of NAS and reduces the antidepressant effects of MAOIs. These data strongly support a role for NAS in mood regulation and in antidepressant-induced therapeutic benefits.

Through a currently unidentified mechanism, NAS may be the cause of the orthostatic hypotension

Orthostatic hypotension

Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...

 seen with clinical treatment of MAOIs. It reduces blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 in rodents, and pinealectomy (the pineal gland

Pineal gland

The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...

 being a major site of NAS and melatonin synthesis) abolishes the hypotensive effects of clorgyline

Clorgyline

Clorgyline is an irreversible and selective inhibitor of monoamine oxidase A that is used in scientific research. It is structurally related to pargyline.- References :...

. Why orthostatic hypotension is commonly seen with MAOIs but not SSRIs (both of which increase NAS levels) however, is unknown.