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Picamilon

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Picamilon
Clinical data
Trade namesНПК ЭХО
Other namesnicotinoyl-GABA
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability50%–88%[2]
Eliminationhalf-life1.5 hours[2]
ExcretionRenal
Identifiers
  • 4-(Pyridine-3-carbonylamino)butanoic acid
CAS Number
PubChemCID
ChemSpider
UNII
CompTox Dashboard(EPA)
ECHA InfoCard100.118.799Edit this at Wikidata
Chemical and physical data
FormulaC10H12N2O3
Molar mass208.217g·mol−1
3D model (JSmol)
  • O=C(NCCCC(=O)O)c1cccnc1
  • InChI=1S/C10H12N2O3/c13-9(14)4-2-6-12-10(15)8-3-1-5-11-7-8/h1,3,5,7H,2,4,6H2,(H,12,15)(H,13,14)checkY
  • Key:NAJVRARAUNYNDX-UHFFFAOYSA-NcheckY
☒NcheckY(what is this?)(verify)

Picamilon(also known asN-nicotinoyl-GABA,pycamilon,andpikamilon) is a drug formed by a synthetic combination ofniacinandγ-aminobutyric acid(GABA). It was developed in theSoviet Unionin 1969[3]and further studied in bothRussia[4]andJapanas aprodrugof GABA.[5]

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 indietary supplements,[6]with five American companies required to remove their picamilon products from the market in November 2015.[7]However, as recently as 2020, picamilon has been found in pharmaceutical dosages in over-the-counter supplements in the US.[8]

Regulation[edit]

In the United States, theFood and Drug Administrationruled in 2015 that picamilon does not fit any of the dietary ingredient categories in theDietary Supplement Health and Education Act of 1994,[7][9]namely that it is not avitamin;adietary mineral;anherbor otherbotanical;anamino 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.[8]

Pharmacology[edit]

Picamilon
Picamilon 20 mg from Russia

A Russian study from 1991 showed that picamilon permeated theblood–brain barrierin cats and increased cerebral blood flow.[10]Further work showed it crosses the blood-brain barrier in mice and rats.[11]It is believed that picamilon ishydrolyzedinto GABA and niacin, similar to the way tocopheryl nicotinate (vitamin E nicotinate) is hydrolyzed.[12]GABA in the brain would activateGABA receptors,which in theory should have ananxiolyticeffect.[13]The second released component,niacin,is avasodilator.[14][15]A 2023 assay study showed that picamilon itself is inactive against 50 biological targets, including GABA receptors, despite being aGABA analogue.[16]

Pharmacokinetics[edit]

Plasma picamilon concentrations are generally in the 500–3000μg/L range during the first few hours after single oral doses of 50–200 mg.[2]It exhibits linear pharmacokinetics with ahalf-lifeof 1–2 hours.[2]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.[2]

References[edit]

  1. ^"Picamilon in Dietary Supplements".FDA.November 29, 2017.RetrievedJune 9,2023.
  2. ^abcdeCui W, Chen X, Zhan Y, Zhang Z, Zhang Y, Zhong D (May 2010). "Determination of picamilon concentration in human plasma by liquid chromatography-tandem mass spectrometry".Journal of Chromatography B.878(15–16): 1181–4.doi:10.1016/j.jchromb.2010.03.013.PMID20359966.
  3. ^Kopelevich VM, Gunar VI (April 1999). "Some approaches to the directed search for new drugs based on nicotinic acid".Pharmaceutical Chemistry Journal.33(4): 177–187.doi:10.1007/BF02509934.S2CID36930437.
  4. ^Mirzoian RS, Gan'shina TS (1989). "[The new cerebrovascular preparation pikamilon]".Farmakologiia i Toksikologiia(in Russian).52(1): 23–6.PMID2707413.
  5. ^Matsuyama K, Yamashita C, Noda A, Goto S, Noda H, Ichimaru Y, et al. (October 1984)."Evaluation of isonicotinoyl-gamma-aminobutyric acid (GABA) and nicotinoyl-GABA as pro-drugs of GABA".Chemical & Pharmaceutical Bulletin.32(10): 4089–95.doi:10.1248/cpb.32.4089.PMID6529802.
  6. ^Avula B, Chittiboyina AG, Sagi S, Wang YH, Wang M, Khan IA, et al. (March 2016)."Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States".Drug Testing and Analysis.8(3–4): 334–43.doi:10.1002/dta.1853.PMID26426301.
  7. ^ab"FDA sends five warning letters over supplements containing picamilon".NutraIngredients-USA, William Reed Business Media. 2 December 2015.Retrieved3 December2015.
  8. ^abCohen PA, Avula B, Wang YH, Zakharevich I, Khan I (June 2021)."Five Unapproved Drugs Found in Cognitive Enhancement Supplements".Neurology. Clinical Practice.11(3): e303–e307.doi:10.1212/CPJ.0000000000000960.PMC8382366.PMID34484905.
  9. ^Welch C."Declaration of Dr. Cara Welch"(PDF).Department of Health and Human Services.Retrieved21 October2015.
  10. ^Dorofeev BF, Kholodov LE (1991). "Pikamilon pharmacokinetics in animals".Farmakologiia i Toksikologiia(in Russian).54(2): 66–9.PMID1884802.
  11. ^Dorofeev BF, Kholodov LE (March 1991). "[Pikamilon pharmacokinetics in animals]".Farmakologiia I Toksikologiia.54(2): 66–69.PMID1884802.
  12. ^Duncan KR, Suzuki YJ (March 2017)."Vitamin E Nicotinate".Antioxidants.6(1): 20.doi:10.3390/antiox6010020.PMID28335380.
  13. ^Shephard RA (June 1987). "Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action".Life Sciences.40(25): 2429–36.doi:10.1016/0024-3205(87)90758-2.PMID2884549.
  14. ^Gille A, Bodor ET, Ahmed K, Offermanns S (2008). "Nicotinic acid: pharmacological effects and mechanisms of action".Annual Review of Pharmacology and Toxicology.48:79–106.doi:10.1146/annurev.pharmtox.48.113006.094746.PMID17705685.
  15. ^Prousky J, Seely D (January 2005)."The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature".Nutrition Journal.4:3.doi:10.1186/1475-2891-4-3.PMC548511.PMID15673472.
  16. ^Santillo MF, Sprando RL (April 2023). "Picamilon, a γ-aminobutyric acid (GABA) analogue and marketed nootropic, is inactive against 50 biological targets".Basic & Clinical Pharmacology & Toxicology.132(4): 355–358.doi:10.1111/bcpt.13836.PMID36668678.

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Picamilon&oldid=1227952353"