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'''Picamilon''' (also known as '''N-nicotinoyl-GABA''', '''pycamilon''', and '''pikamilon''') is a drug formed by a synthetic combination of [[niacin]] and [[Gamma-aminobutyric acid|GABA]]. It was developed in the [[Soviet Union]] in 1969 by the All-Union Vitamins Scientific Research Institute<ref name=" Some approaches to the directed search for new drugs based on nicotinic acid">{{cite journal | author = 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 | pmid = | doi = 10.1007/BF02509934 | url = http://www.springerlink.com/content/r8430r0l4x596027/ }}</ref> and further studied in both [[Russia]]<ref name="pmid2707413">{{cite journal | author = Mirzoian RS, Gan'shina TS | title = [The new cerebrovascular preparation pikamilon] | language = Russian | journal = Farmakologiia i toksikologiia | volume = 52 | issue = 1 | pages = 23–6 | year = 1989 | pmid = 2707413 | doi = | issn = }}</ref> and [[Japan]] as a [[prodrug]] of GABA.<ref name="pmid6529802">{{cite journal | author = 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 = Chem. Pharm. Bull. | volume = 32 | issue = 10 | pages = 4089–95 |date=October 1984 | pmid = 6529802 | doi = 10.1248/cpb.32.4089| url = http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=cpb1958&cdvol=32&noissue=10&startpage=4089 }}</ref>
'''Picamilon''' (also known as '''N-nicotinoyl-GABA''', '''pycamilon''', and '''pikamilon''') is a drug formed by a synthetic combination of [[niacin]] and [[Gamma-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 | author = 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 | pmid = | doi = 10.1007/BF02509934 | url = http://www.springerlink.com/content/r8430r0l4x596027/ }}</ref> and further studied in both [[Russia]]<ref name="pmid2707413">{{cite journal | author = Mirzoian RS, Gan'shina TS | title = [The new cerebrovascular preparation pikamilon] | language = Russian | journal = Farmakologiia i toksikologiia | volume = 52 | issue = 1 | pages = 23–6 | year = 1989 | pmid = 2707413 | doi = | issn = }}</ref> and [[Japan]] as a [[prodrug]] of GABA.<ref name="pmid6529802">{{cite journal | author = 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 = Chem. Pharm. Bull. | volume = 32 | issue = 10 | pages = 4089–95 |date=October 1984 | pmid = 6529802 | doi = 10.1248/cpb.32.4089| url = http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=cpb1958&cdvol=32&noissue=10&startpage=4089 }}</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.<ref>{{cite web | url = http://www.livescience.com/52353-supplements-unapproved-drugs-vinpocetine-picamilon.html | title = Some Brain & Workout Supplements Contain Unapproved Drugs | date = October 1, 2015 | publisher = Live Science}}</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 as an adulterating agent in [[dietary supplements]], 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/?utm_source=newsletter_daily&utm_medium=email&utm_campaign=03-Dec-2015&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|accessdate=3 December 2015}}</ref>


==Mechanism of action and potential therapeutic applications==
==Mechanism of action and potential therapeutic applications==
Picamilon is able to cross the [[blood–brain barrier]]<ref name="pmid1884802">{{cite journal | author = Dorofeev BF, Kholodov LE | title = [Pikamilon pharmacokinetics in animals] | language = Russian | journal = Farmakologiia i toksikologiia | volume = 54 | issue = 2 | pages = 66–9 | year = 1991 | pmid = 1884802 | doi = | issn = }}</ref> and then is [[hydrolyzed]] into GABA and niacin.<ref>{{cite web|url=http://picamilon.org/|title=Technical Description of Picamilon}}</ref> The released GABA in theory would activate [[GABA receptor]]s potentially producing an [[anxiolytic]] response.<ref name="pmid2884549">{{cite journal | author = Shephard RA | title = Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action | journal = Life Sci. | volume = 40 | issue = 25 | pages = 2429–36 |date=June 1987 | pmid = 2884549 | doi = 10.1016/0024-3205(87)90758-2| url = }}</ref> The second released component, niacin acts as a strong [[vasodilator]],<ref name="pmid17705685">{{cite journal | author = Gille A, Bodor ET, Ahmed K, Offermanns S | title = Nicotinic acid: pharmacological effects and mechanisms of action | journal = Annu. Rev. Pharmacol. Toxicol. | volume = 48 | issue = | pages = 79–106 | year = 2008 | pmid = 17705685 | doi = 10.1146/annurev.pharmtox.48.113006.094746 | url = }}</ref> which might be useful for the treatment of [[migraine]] headaches.<ref name="pmid2625145">{{cite journal | author = Pukhal'skaia TG, Maĭsov NI, Mirzoian RS | title = [The effect of antimigraine preparations on serotonin transport in the brain synaptosomes of rats] | language = Russian | journal = Farmakol Toksikol | volume = 52 | issue = 6 | pages = 39–43 | year = 1989 | pmid = 2625145 | doi = | url = | issn = }}</ref><ref name="pmid15673472">{{cite journal | author = 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 = Nutr J | volume = 4 | issue = | pages = 3 | year = 2005 | pmid = 15673472 | doi = 10.1186/1475-2891-4-3 | url = | pmc = 548511 }}</ref>
One study in animals showed that picamilon penetrated the [[blood–brain barrier]]<ref name="pmid1884802">{{cite journal | author = Dorofeev BF, Kholodov LE | title = [Pikamilon pharmacokinetics in animals] | language = Russian | journal = Farmakologiia i toksikologiia | volume = 54 | issue = 2 | pages = 66–9 | year = 1991 | pmid = 1884802 | doi = | issn = }}</ref> and then is [[hydrolyzed]] into GABA and niacin.<ref>{{cite web|url=http://picamilon.org/|title=Technical Description of Picamilon}}</ref> The released GABA in theory would activate [[GABA receptor]]s potentially producing an [[anxiolytic]] response.<ref name="pmid2884549">{{cite journal | author = Shephard RA | title = Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action | journal = Life Sci. | volume = 40 | issue = 25 | pages = 2429–36 |date=June 1987 | pmid = 2884549 | doi = 10.1016/0024-3205(87)90758-2| url = }}</ref> The second released component, [[niacin]], potentially is a [[vasodilator]].<ref name="pmid17705685">{{cite journal | author = Gille A, Bodor ET, Ahmed K, Offermanns S | title = Nicotinic acid: pharmacological effects and mechanisms of action | journal = Annu. Rev. Pharmacol. Toxicol. | volume = 48 | issue = | pages = 79–106 | year = 2008 | pmid = 17705685 | doi = 10.1146/annurev.pharmtox.48.113006.094746 | url = }}</ref><ref name="pmid15673472">{{cite journal | author = 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 = Nutr J | volume = 4 | issue = | pages = 3 | year = 2005 | pmid = 15673472 | doi = 10.1186/1475-2891-4-3 | url = | pmc = 548511 }}</ref>


==Detection in biological fluids==
==Detection in biological fluids==
Plasma picamilon concentrations are generally in the 500–3000 μg/L range during the first few hours after single oral doses of 50-200 mg. The plasma elimination half-life ranges from 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. The presence of picamilon in biofluids may be accomplished by one of a variety of chromatographic methods.<ref>W. Cui, X. Chen, Y. Zhan et al. Determination of picamilon concentration in human plasma by liquid chromatography-tandem mass spectrometry. J. Chrom. B 878: 1181–1184, 2010.</ref><ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 10th edition, Biomedical Publications, Seal Beach, CA, 2014, p. 1639-1640.</ref>
Plasma picamilon concentrations are generally in the 500–3000 μg/L range during the first few hours after single oral doses of 50-200 mg with a [[half-life]] of 1-2 hours.<ref name="cui">W. Cui, X. Chen, Y. Zhan et al. Determination of picamilon concentration in human plasma by liquid chromatography-tandem mass spectrometry. J. Chrom. B 878: 1181–1184, 2010</ref> 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"/>


==Medical use in Russia==
[[File:Picamilon.jpg|thumb|alt=Picamilon|Picamilon 20 mg from Russia]]
[[File:Picamilon.jpg|thumb|alt=Picamilon|Picamilon 20 mg from Russia]]
In Russia, Picamilon is used for treatment of these illness.<ref name="RLS">
{{cite web
|url=http://www.rlsnet.ru/tn_index_id_5545.htm
|title=Пикамилон
|work=Энциклопедия лекарств
|publisher=Регистр лекарственных средств России}}</ref>
# Violations of cerebral blood flow (ischemic acute, subacute and rehabilitation period of [[ischemic stroke]], chronic insufficiency of cerebral blood flow);
# [[Vasoneurosis]];
# [[Asthenia]] (weakness);
# [[Major depressive disorder|Depression]];
# Senile [[psychosis]];
# Alcohol (period of [[abstinence]]), acute [[alcohol intoxication]];
# [[Migraine]]
# [[Craniocerebral trauma]]
# [[:Category:Neurological infections|Neuroinfections]];
# Primary [[Glaucoma#Signs and symptoms|open-angle glaucoma]] (for stabilization of visual function).


==Regulation==
==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>{{cite web|last1=Welch|first1=Cara|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|accessdate=21 October 2015}}</ref> namely that it is not a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above. This led to the removal of picamilon from various supplements manufactured in the US.<ref>{{cite web|last1=Roberto|first1=Mike|title=Picamilon Under FDA Attack|url=https://blog.priceplow.com/supplement-news/picamilon-fda|website=PricePlow|accessdate=21 October 2015|date=13 October 2015}}</ref>
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|last1=Welch|first1=Cara|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|accessdate=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. This led to the removal of picamilon from various supplements manufactured in the US.<ref name="nutra"/><ref>{{cite web|last1=Roberto|first1=Mike|title=Picamilon Under FDA Attack|url=https://blog.priceplow.com/supplement-news/picamilon-fda|website=PricePlow|accessdate=21 October 2015|date=13 October 2015}}</ref>


==References==
==References==
Line 83: Line 66:
== External links ==
== External links ==
* {{MeshName|nicotinoyl-GABA}}
* {{MeshName|nicotinoyl-GABA}}
* {{cite web | url = http://www.picamilon.net/picamilon/picamilon-intro.htm | title = Picamilon introduction | author = A.L. Karayev | authorlink = | coauthors = | date = | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-05-28}}
* [[Erowid]] [http://www.erowid.org/experiences/subs/exp_Picamilon.shtml Picamilon experience reports]



{{GABAergics}}
{{GABAergics}}

Revision as of 20:34, 3 December 2015

Picamilon
Clinical data
Trade namesНПК ЭХО
Other namesnicotinoyl-GABA
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability50%–88%
Elimination half-life30 minutes
ExcretionRenal
Identifiers
  • 4-(Pyridine-3-carbonylamino)butanoic acid
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.118.799 Edit this at Wikidata
Chemical and physical data
FormulaC10H12N2O3
Molar mass208.214 g/mol g·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-N checkY
 ☒NcheckY (what is this?)  (verify)

Picamilon (also known as N-nicotinoyl-GABA, pycamilon, and pikamilon) is a drug formed by a synthetic combination of niacin and GABA. It was developed in the Soviet Union in 1969[1] and further studied in both Russia[2] and Japan as a prodrug of GABA.[3]

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 as an adulterating agent in dietary supplements, with five American companies required to remove their picamilon products from the market in November, 2015.[4]

Mechanism of action and potential therapeutic applications

One study in animals showed that picamilon penetrated the blood–brain barrier[5] and then is hydrolyzed into GABA and niacin.[6] The released GABA in theory would activate GABA receptors potentially producing an anxiolytic response.[7] The second released component, niacin, potentially is a vasodilator.[8][9]

Detection in biological fluids

Plasma picamilon concentrations are generally in the 500–3000 μg/L range during the first few hours after single oral doses of 50-200 mg with a half-life of 1-2 hours.[10] 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.[10]

Picamilon
Picamilon 20 mg from Russia

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,[4][11] 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. This led to the removal of picamilon from various supplements manufactured in the US.[4][12]

References

  1. ^ 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.
  2. ^ Mirzoian RS, Gan'shina TS (1989). "[The new cerebrovascular preparation pikamilon]". Farmakologiia i toksikologiia (in Russian). 52 (1): 23–6. PMID 2707413.
  3. ^ Matsuyama K, Yamashita C, Noda A, Goto S, Noda H, Ichimaru Y, Gomita Y (October 1984). "Evaluation of isonicotinoyl-gamma-aminobutyric acid (GABA) and nicotinoyl-GABA as pro-drugs of GABA". Chem. Pharm. Bull. 32 (10): 4089–95. doi:10.1248/cpb.32.4089. PMID 6529802.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b c "FDA sends five warning letters over supplements containing picamilon". NutraIngredients-USA.com, William Reed Business Media. 2 December 2015. Retrieved 3 December 2015.
  5. ^ Dorofeev BF, Kholodov LE (1991). "[Pikamilon pharmacokinetics in animals]". Farmakologiia i toksikologiia (in Russian). 54 (2): 66–9. PMID 1884802.
  6. ^ "Technical Description of Picamilon".
  7. ^ Shephard RA (June 1987). "Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action". Life Sci. 40 (25): 2429–36. doi:10.1016/0024-3205(87)90758-2. PMID 2884549.
  8. ^ Gille A, Bodor ET, Ahmed K, Offermanns S (2008). "Nicotinic acid: pharmacological effects and mechanisms of action". Annu. Rev. Pharmacol. Toxicol. 48: 79–106. doi:10.1146/annurev.pharmtox.48.113006.094746. PMID 17705685.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Prousky J, Seely D (2005). "The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature". Nutr J. 4: 3. doi:10.1186/1475-2891-4-3. PMC 548511. PMID 15673472.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ a b W. Cui, X. Chen, Y. Zhan et al. Determination of picamilon concentration in human plasma by liquid chromatography-tandem mass spectrometry. J. Chrom. B 878: 1181–1184, 2010
  11. ^ Welch, Cara. "Declaration of Dr. Cara Welch" (PDF). Department of Health and Human Services. Retrieved 21 October 2015.
  12. ^ Roberto, Mike (13 October 2015). "Picamilon Under FDA Attack". PricePlow. Retrieved 21 October 2015.
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