Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Picamilon: Difference between pages

{{short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 464206196

| IUPAC_name = 4-(Pyridine-3-carbonylamino)butanoic acid

| tradename = НПК ЭХО

| pregnancy_US =

| legal_US = Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in [[dietary supplement]]s, [[food]], or [[medicine]] is unlawful; otherwise uncontrolled.<ref>{{Cite web |date=November 29, 2017 |title=Picamilon in Dietary Supplements |url=https://www.fda.gov/food/dietary-supplement-ingredient-directory/picamilon-dietary-supplements |access-date=June 9, 2023 |website=[[FDA]]}}</ref>

| legal_status = [[Russia|RU]]: OTC

| bioavailability = 50%&ndash;88%<ref name="cui"/>

| elimination_half-life = 1.5 hours<ref name="cui"/>

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 34562-97-5

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = 0S5N9SEK4N

'''Picamilon''' (also known as '''''N''-nicotinoyl-GABA''', '''pycamilon''', and '''pikamilon''') is a drug formed by a synthetic combination of [[Niacin (substance)|niacin]] and [[Gamma-aminobutyric acid|γ-aminobutyric acid]] (GABA). It was developed in the [[Soviet Union]] in 1969<ref name=" Some approaches to the directed search for new drugs based on nicotinic acid">{{cite journal | vauthors = Kopelevich VM, Gunar VI | title = Some approaches to the directed search for new drugs based on nicotinic acid | journal = Pharmaceutical Chemistry Journal | volume = 33 | issue = 4 | pages = 177–187 |date=April 1999 | doi = 10.1007/BF02509934 | s2cid = 36930437 }}</ref> and further studied in both [[Russia]]<ref name="pmid2707413">{{cite journal | vauthors = Mirzoian RS, Gan'shina TS | title = [The new cerebrovascular preparation pikamilon] | language = ru | journal = Farmakologiia i Toksikologiia | volume = 52 | issue = 1 | pages = 23–6 | year = 1989 | pmid = 2707413 }}</ref> and [[Japan]] as a [[prodrug]] of GABA.<ref name="pmid6529802">{{cite journal | vauthors = Matsuyama K, Yamashita C, Noda A, Goto S, Noda H, Ichimaru Y, Gomita Y | title = Evaluation of isonicotinoyl-gamma-aminobutyric acid (GABA) and nicotinoyl-GABA as pro-drugs of GABA | journal = Chemical & Pharmaceutical Bulletin | volume = 32 | issue = 10 | pages = 4089–95 | date = October 1984 | pmid = 6529802 | doi = 10.1248/cpb.32.4089 | doi-access = free }}</ref>

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]],<ref name="DTA2015">{{cite journal | vauthors = Avula B, Chittiboyina AG, Sagi S, Wang YH, Wang M, Khan IA, Cohen PA | title = Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States | journal = Drug Testing and Analysis | volume = 8 | issue = 3–4 | pages = 334–43 | date = March 2016 | pmid = 26426301 | doi = 10.1002/dta.1853 | doi-access = free }}</ref> with five American companies required to remove their picamilon products from the market in November 2015.<ref name="nutra">{{cite web | url = http://www.nutraingredients-usa.com/Regulation/FDA-sends-five-warning-letters-over-supplements-containing-picamilon/?c=7InNqGv0AjdjxWpyk%2BfGQw%3D%3D&p2= | title = FDA sends five warning letters over supplements containing picamilon | date = 2 December 2015 | publisher = NutraIngredients-USA.com, William Reed Business Media|access-date=3 December 2015}}</ref> However, as recently as 2020, picamilon has been found in pharmaceutical dosages in over-the-counter supplements in the US.<ref name="neuro">{{cite journal | vauthors = Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I | title = Five Unapproved Drugs Found in Cognitive Enhancement Supplements | journal = Neurology. Clinical Practice | volume = 11 | issue = 3 | pages = e303–e307 | date = June 2021 | pmid = 34484905 | pmc = 8382366 | doi = 10.1212/CPJ.0000000000000960 }}</ref>

== Regulation ==

In the United States, the [[Food and Drug Administration]] ruled in 2015 that picamilon does not fit any of the dietary ingredient categories in the [[Dietary Supplement Health and Education Act of 1994]],<ref name="nutra"/><ref>{{cite web | vauthors = Welch C | title = Declaration of Dr. Cara Welch|url=https://blog.priceplow.com/wp-content/uploads/Picamilon-FDA_Ruling-20150928.pdf|publisher=Department of Health and Human Services|access-date=21 October 2015}}</ref> namely that it is not a [[vitamin]]; a [[dietary mineral]]; an [[herb]] or other [[botanical]]; an [[amino acid]]; 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.<ref name="neuro"/>

== Pharmacology ==

[[File:Picamilon.jpg|thumb|alt=Picamilon|Picamilon 20 mg from Russia]]

A Russian study from 1991 showed that picamilon permeated the [[blood–brain barrier]] in cats and increased cerebral blood flow.<ref name="pmid1884802">{{cite journal | vauthors = Dorofeev BF, Kholodov LE | title = Pikamilon pharmacokinetics in animals | language = ru | journal = Farmakologiia i Toksikologiia | volume = 54 | issue = 2 | pages = 66–9 | year = 1991 | pmid = 1884802 }}</ref> Further work showed it crosses the blood-brain barrier in mice and rats.<ref>{{cite journal | vauthors = Dorofeev BF, Kholodov LE | title = [Pikamilon pharmacokinetics in animals] | journal = Farmakologiia I Toksikologiia | volume = 54 | issue = 2 | pages = 66–69 | date = March 1991 | pmid = 1884802 }}</ref> It is believed that picamilon is [[hydrolyzed]] into GABA and niacin, similar to the way tocopheryl nicotinate (vitamin E nicotinate) is hydrolyzed.<ref>{{cite journal | vauthors = Duncan KR, Suzuki YJ | title = Vitamin E Nicotinate | journal = Antioxidants | volume = 6 | issue = 1 | pages = 20 | date = March 2017 | pmid = 28335380 | doi = 10.3390/antiox6010020 | doi-access = free }}</ref> GABA in the brain would activate [[GABA receptor]]s, which in theory should have an [[anxiolytic]] effect.<ref name="pmid2884549">{{cite journal | vauthors = Shephard RA | title = Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action | journal = Life Sciences | volume = 40 | issue = 25 | pages = 2429–36 | date = June 1987 | pmid = 2884549 | doi = 10.1016/0024-3205(87)90758-2 }}</ref> The second released component, [[Niacin (substance)|niacin]], is a [[vasodilator]].<ref name="pmid17705685">{{cite journal | vauthors = Gille A, Bodor ET, Ahmed K, Offermanns S | title = Nicotinic acid: pharmacological effects and mechanisms of action | journal = Annual Review of Pharmacology and Toxicology | volume = 48 | pages = 79–106 | year = 2008 | pmid = 17705685 | doi = 10.1146/annurev.pharmtox.48.113006.094746 }}</ref><ref name="pmid15673472">{{cite journal | vauthors = Prousky J, Seely D | title = The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature | journal = Nutrition Journal | volume = 4 | pages = 3 | date = January 2005 | pmid = 15673472 | pmc = 548511 | doi = 10.1186/1475-2891-4-3 | doi-access = free }}</ref> A 2023 assay study showed that picamilon itself is inactive against 50 biological targets, including GABA receptors, despite being a [[GABA analogue]].<ref>{{cite journal | vauthors = Santillo MF, Sprando RL | title = Picamilon, a γ-aminobutyric acid (GABA) analogue and marketed nootropic, is inactive against 50 biological targets | journal = Basic & Clinical Pharmacology & Toxicology | volume = 132 | issue = 4 | pages = 355–358 | date = April 2023 | pmid = 36668678 | doi = 10.1111/bcpt.13836 }}</ref>

== Pharmacokinetics ==

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&nbsp;mg.<ref name="cui">{{cite journal | vauthors = Cui W, Chen X, Zhan Y, Zhang Z, Zhang Y, Zhong D | title = Determination of picamilon concentration in human plasma by liquid chromatography-tandem mass spectrometry | journal = Journal of Chromatography B | volume = 878 | issue = 15–16 | pages = 1181–4 | date = May 2010 | pmid = 20359966 | doi = 10.1016/j.jchromb.2010.03.013 }}</ref> It exhibits linear pharmacokinetics with a [[half-life]] of 1–2 hours.<ref name="cui"/> As discussed previously, 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.<ref name="cui"/>

== See also ==

* [[List of Russian drugs]]

== References ==

{{Reflist|2}}

== External links ==

* {{MeshName|nicotinoyl-GABA}}

{{GABAergics}}

[[Category:Anxiolytics]]

[[Category:Nicotinamides]]

[[Category:GABA analogues]]

[[Category:Gamma-Amino acids]]

[[Category:Neurotransmitter precursors]]

[[Category:Russian drugs]]

[[Category:Prodrugs]]

[[Category:Drugs in the Soviet Union]]