Picamilon (also known as ''N''-nicotinoyl-GABA, pycamilon, and pikamilon) is a drug formed by a synthetic combination of

niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

and γ-aminobutyric acid (GABA). It was developed in the

Soviet Union The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, ...

in 1969 and further studied in both

Russia Russia (, , ), or the Russian Federation, is a transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-eigh ...

and Japan as a prodrug of GABA. In Russia, picamilon is sold as a prescription drug. The rights to the drug belong to the Russian pharmaceutical company NPK ECHO ("НПК ЭХО"). It is not approved for sale in the United States and has been deemed an adulterating agent in

dietary supplements A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

, with five American companies required to remove their picamilon products from the market in November, 2015. However, as recently as 2020, picamilon has been found in pharmaceutical dosages in over-the-counter supplements in the US.

Mechanism of action and potential therapeutic applications

One study in animals showed that picamilon permeated the blood–brain barrier and then is

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

into GABA and niacin. The released GABA in theory would activate

GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

s potentially producing an

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

response. The second released component,

, is a

vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...

Detection in biological fluids

Plasma picamilon concentrations are generally in the 500–3000 ''μ''g/L range during the first few hours after single oral doses of 50–200 mg with a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of 1–2 hours. The drug undergoes hydrolysis to GABA and nicotinic acid. Urinary excretion of parent drug and the two metabolites accounts for up to 79% of a single dose. Picamilon

Regulation

In the United States, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

ruled in 2015 that picamilon does not fit any of the dietary ingredient categories in the

Dietary Supplement Health and Education Act of 1994 The Dietary Supplement Health and Education Act of 1994 ("DSHEA"), is a 1994 statute of United States Federal legislation which defines and regulates dietary supplements. Under the act, supplements are regulated by the FDA for Good Manufacturing ...

, namely that it is not a

vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nut ...

; a

dietary mineral In the context of nutrition, a mineral is a chemical element required as an essential nutrient by organisms to perform functions necessary for life. However, the four major structural elements in the human body by weight (oxygen, hydrogen, carbon, ...

; an

herb In general use, herbs are a widely distributed and widespread group of plants, excluding vegetables and other plants consumed for macronutrients, with savory or aromatic properties that are used for flavoring and garnishing food, for medicina ...

or other

botanical Botany, also called plant science (or plant sciences), plant biology or phytology, is the science of plant life and a branch of biology. A botanist, plant scientist or phytologist is a scientist who specialises in this field. The term "botany ...

; an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

; a dietary substance for use by humans to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above that had been marketed in the United States before 1994. Despite the FDA ruling, picamilon remains an ingredient in supplements marketed as nootropics in the US.

References

External links

* {{GABAergics Anxiolytics Nicotinamides GABA analogues GABAA receptor agonists GABAA-rho receptor agonists GABAB receptor agonists Russian drugs Prodrugs Drugs in the Soviet Union