Emoxypine: Difference between revisions

{{Short description|Chemical compound}}

{{distinguish|Amoxapine}}

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

{{Infobox drug

| verifiedrevid = 451921411

| IUPAC_name = 2-Ethyl-6-methyl-3-hydroxypyridine

| image2 = Emoxypine ball-and-stick.png

| tradename = Mexidol

| pregnancy_category =

| legal_status = RU: Rx only

| legal_US = Unscheduled; not FDA approved

| routes_of_administration = Oral & IV

| bioavailability =

| metabolism =

| elimination_half-life = 2-2.6 h

| excretion =

| index_label =

| index2_label =

| ATC_suffix =

| synonyms = Emoxipine, Emoxypin, Epigid, 6-Methyl-2-ethyl-3-hydroxypyridine

| CAS_number = 2364-75-2

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = V247P5H4E1

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| smiles2 = Oc1ccc(nc1CC)C

| chemical_formula =

| C=8 | H=11 | N=1 | O=1

| melting_notes = <ref>{{cite journal | vauthors = Gruber W | year = 1953 | title = Synthesis of 3-Hydroxy-2-alkylpyridines | journal = Canadian Journal of Chemistry | volume = 31 | issue = 6 | pages = 564–568 | doi = 10.1139/v53-079 | doi-access = free }}</ref>

'''Emoxypine''' (2-ethyl-6-methyl-3-hydroxypyridine), also known as '''Mexidol''' or '''Mexifin''', a [[succinate]] [[salt (chemistry)|salt]], is chemical compound which is claimed by its manufacturer, the Russian company Pharmasoft Pharmaceuticals, to have antioxidant and [[actoprotector]] properties.<ref>{{Cite web |url=http://www.mexidol.ru/en |title=mexidol.ru, Pharmasoft Website |access-date=2011-04-27 |archive-url=https://web.archive.org/web/20110410103710/http://www.mexidol.ru/en/ |archive-date=2011-04-10 |url-status=dead }}</ref><ref>{{Cite journal | vauthors = Yakovlev IY |date=2013 |title=Механізми актопротекторної дії похідних янтарної кислоти |trans-title=Mechanisms of actoprotective action of succinic acid's derivatives |language=uk |journal=Лікарська справа |issue=3 |pages=78–85 |pmid=25016753 |url=https://liksprava.com/index.php/journal/issue/view/15/3-2013-FULL-PDF }}</ref> Its chemical structure resembles that of [[pyridoxine]] (a type of [[vitamin B6|vitamin B₆]]).

==History==

Emoxypine was first synthesized by L.D. Smirnov and K.M. Dumayev, then studied and developed in the Russian Institute of Pharmacology, Russian Academy of Medical Sciences and Russian Scientific Center of Bioactive Substances Safety.<ref name=item102573>{{cite web | vauthors = Voronina TA | work = Institute of Pharmacology | publisher = Russian Academy of Medical Sciences | location = Moscow, Russia | title = ANTIOXIDANT MEXIDOL. The main neuropsychotropic effects and the mechanism of action | url = http://www.mexidol.ru/en/pro/library/farmacology/item102573 | archive-url = https://web.archive.org/web/20131105055936/http://www.mexidol.ru/en/pro/library/farmacology/item102573 | archive-date=2013-11-05 }}</ref> Its research and use has been largely isolated to former soviet states, with little interest from other countries.<ref>{{cite journal | vauthors = Gupta DS, Bagwe Parab S, Kaur G | title = Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications | journal = Current Research in Pharmacology and Drug Discovery | volume = 3 | pages = 100121 | date = 1 January 2022 | pmid = 35992374 | doi = 10.1016/j.crphar.2022.100121 | pmc = 9389226 }}</ref>

==Use==

Emoxypine is widely used in Russia, primarily for its anti-oxidant properties claimed by the manufacturer. It purportedly exercises [[anxiolytic]],<ref>{{cite journal | vauthors = Volchegorskii IA, Miroshnichenko IY, Rassokhina LM, Faizullin RM, Malkin MP, Pryakhina KE, Kalugina AV | s2cid = 6052275 | title = Comparative analysis of the anxiolytic effects of 3-hydroxypyridine and succinic acid derivatives | journal = Bulletin of Experimental Biology and Medicine | volume = 158 | issue = 6 | pages = 756–61 | date = April 2015 | pmid = 25894772 | doi = 10.1007/s10517-015-2855-3 }}</ref><ref>{{cite journal | vauthors = Rumyantseva SA, Fedin AI, Sokhova ON |s2cid=39971165 |title=Antioxidant Treatment of Ischemic Brain Lesions |journal=Neuroscience and Behavioral Physiology |date=October 2012 |volume=42| issue=8 |pages=842–845 |doi=10.1007/s11055-012-9646-3}}</ref> anti-stress, anti-[[alcohol (drug)|alcohol]], [[anticonvulsant]], [[nootropic]], [[neuroprotective]] and [[anti-inflammatory]] action.{{Citation needed|date=March 2013}} Emoxypine presumably improves [[cerebral blood flow|cerebral blood circulation]], inhibits [[thrombocyte]] aggregation, lowers [[cholesterol]] levels, has cardioprotective and [[atherosclerosis|antiatherosclerotic action]].<ref name=item102573/> Compound's iron chelating property in vitro, shows potential in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders.<ref>{{cite journal | vauthors = Gupta DS, Bagwe Parab S, Kaur G | title = Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications | journal = Current Research in Pharmacology and Drug Discovery | volume = 3 | pages = 100121 | date = 2022 | pmid = 35992374 | pmc = 9389226 | doi = 10.1016/j.crphar.2022.100121 }}</ref>

==Mechanism of action==

Emoxypine's [[mechanism of action]] is believed to be its antioxidant and membrane-protective effects with the following key components:<ref name=item102573/><ref>{{cite report | vauthors = Dumayev KM, Voronina TA, Smirnov LD | title = Antioxidants in the prophylaxis and therapy of CNS pathologies. | location = Moscow | date = 1995 }}{{page needed|date=April 2023}}</ref>{{medical citation needed|date=March 2013}}

* Emoxypine inhibits oxidation of biomembrane lipids.

* Increases the activity of [[antioxidant]] enzymes, specifically that of [[superoxide dismutase]], responsible for the formation and consumption of [[lipid peroxidation|lipid peroxides]] and active oxygen forms.

* Inhibits free radicals during the synthesis of [[prostaglandin]] catalyzed [[cyclooxygenase]] and [[lipoxygenase]], increases the correlation [[prostacyclin]]/ [[thromboxane A2]] and blocks the [[leukotriene]] formation.

* Increases the content of polar fraction of lipids ([[phosphatidyl serine]] and [[phosphatidyl inositol]]) and reduces the cholesterol/[[phospholipid]]s ratio which proves its lipid-regulatory properties; shifts structure transition into the low temperature zones, that is provokes the reduction of membrane viscosity and the increase of its fluidity, increases lipid-protein ratio.

* Modulates the activity of membrane-bound enzymes: [[phosphodiesterase]], [[cyclic nucleotide]]s, [[adenylate cyclase]], aldoreductase, [[acetylcholinesterase]].

* Modulates the receptor complexes of the brain membranes, i.e. [[benzodiazepine]], [[GABA]], [[acetylcholine]] receptors by increasing their binding ability.

* Stabilizes [[biomembrane]]s, i.e. membrane structures of blood cells - [[erythrocyte]]s and thrombocytes during their haemolysis or mechanical injury accompanied by the formation of free radicals.

* Changes the monoamine level and increases the [[dopamine]] content in the brain.<ref name=item102573/><ref>{{cite journal | vauthors = Kucherianu VG | title = [Mexidol potentiates antiparkinsonian effect of L-DOPA in MPTP-induced parkinsonism model] | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 64 | issue = 1 | pages = 22–5 | date = January 2001 | pmid = 11544797 }}</ref>

==Clinical study==

One non-blinded non-randomized study determined the effectiveness of emoxypine in 205 patients with clinical manifestations of [[lumbosacral radiculopathy]] (LSR). Patients were divided into two groups, and further were divided into subgroups depending on the presence of motor disturbances. All patients received a course of conventional medical treatment and physiotherapy; main group additionally received emoxypine. Thereafter, clinical-neurological control of long-term results of treatment in subgroups of patients was performed. The results showed that the use of emoxypine in the combined therapy of patients with LSR led to significant and persistent reduction of severity of pain syndrome and rapid recovery of function of spinal roots and [[peripheral nerve]]s compared with conventional therapy.<ref name=item102573/><ref>{{cite journal | vauthors = Likhacheva EB, Sholomov II | title = [Clinical and immunological assessment of efficacy of mexidol in the treatment of lumbosacral radiculopathy] | journal = Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova | volume = 106 | issue = 10 | pages = 52–7 | year = 2006 | pmid = 17117675 }}</ref>

==Legal status==

Emoxypine is an uncontrolled substance in the United States meaning it is legal to possess without a license or prescription. Use of Emoxypine in food, supplements, and drugs is unlawful and constitutes an act of misbranding. It is considered a "New Drug" as defined by 21 U.S. Code § 321(p)(1).

==References==

{{Reflist}}

==External links==

*{{Commons category-inline}}

{{Anxiolytics}}

[[Category:Anxiolytics]]

[[Category:Hydroxypyridines]]

[[Category:Nootropics]]

[[Category:Russian drugs]]