Picamilon (also known asN-nicotinoyl-GABA,pycamilon, andpikamilon) is a drug formed by a synthetic combination ofniacin andγ-aminobutyric acid (GABA). It was developed in theSoviet Union in 1969[3] and further studied in bothRussia[4] andJapan as aprodrug of 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]
In the United States, theFood and Drug Administration ruled 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; anherb or 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]
A Russian study from 1991 showed that picamilon permeated theblood–brain barrier in 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 ishydrolyzed into 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 ananxiolytic effect.[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]
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-life of 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]
^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.
^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.
^Mirzoian RS, Gan'shina TS (1989). "[The new cerebrovascular preparation pikamilon]".Farmakologiia i Toksikologiia (in Russian).52 (1):23–6.PMID2707413.
^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.
^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.
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