{{Short description|Stimulant drug}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | verifiedrevid = 444178004 | image = Mesocarb.svg | image_class = skin-invert-image | width = 250px
<!-- Clinical data --> | tradename = Sidnocarb, Sydnocarb, Synocarb | legal_BR = B1 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}</ref> | legal_CA = Schedule III | legal_UK = Class C | legal_DE = Anlage II | legal_US = Schedule I | legal_status = | routes_of_administration = Oral | class = Atypical dopamine reuptake inhibitor
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = Hepatic | metabolites = | elimination_half-life = | excretion = Renal
<!-- Identifiers --> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 34262-84-5 | ATC_prefix = None | PubChem = 9551611 | PubChemSubstance = 497621129 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 16736988 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = UMT8MP2NDU | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D12716 | synonyms = Fensidnimine; Pharmaneocarb; Sydnocarbum; MLR-1017; ''N''-Phenylcarbamoyl-3-(β-phenylisopropyl)sydnonimine; 3-(β-Phenylisopropyl)-''N''-phenylcarbamoylsydnonimine
<!-- Chemical data --> | IUPAC_name = 5-(Phenylcarbamoylimino)-3-(1-phenylpropan-2-yl)-5''H''-1,2,3-oxadiazol-3-ium-2-ide | C=18 | H=18 | N=4 | O=2 | SMILES = O=C(\N=C1/C=[N+](\[N-]O1)C(C)Cc2ccccc2)Nc3ccccc3 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C18H18N4O2/c1-14(12-15-8-4-2-5-9-15)22-13-17(24-21-22)20-18(23)19-16-10-6-3-7-11-16/h2-11,13-14H,12H2,1H3,(H,19,23)/b20-17+ | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DMHQLXUFCQSQQQ-LVZFUZTISA-N }} <!-- Definition and medical uses --> '''Mesocarb''', sold under the brand name '''Sidnocarb''' or '''Sydnocarb''' and known by the developmental code name '''MLR-1017''', is a psychostimulant medication which has been used in the treatment of psychiatric disorders and for a number of other indications in the Soviet Union and Russia.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA774 | access-date=16 September 2024 | page=774}}</ref><ref name="IndexNominum2000">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum 2000: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2000 | isbn=978-3-88763-075-1 | url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA655 | access-date=16 September 2024 | page=655}}</ref><ref name="FroestlPfeiferMuhs2013">{{cite journal | vauthors = Froestl W, Pfeifer A, Muhs A | title = Cognitive enhancers (nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. disease-modifying drugs | journal = J Alzheimers Dis | volume = 34 | issue = 1 | pages = 1–114 | date = 2013 | pmid = 23186990 | doi = 10.3233/JAD-121729 | url = https://www.researchgate.net/publication/236142322 | quote=MLR-1017 (mesocarb, sydnocarb, sidnocarb, Melior Pharmaceuticals, Exton, PA) (Fig. 4) is a dopamine transporter inhibitor for the potential treatment of ADHD and levodopa-induced side effects in PD. The drug was previously launched in Russia [271, 272] (Thomson Reuters Pharma, update of April 12, 2012).}}</ref><ref name="Macolino-KaneCiallellaLipinski2017">{{cite book | vauthors = Macolino-Kane CM, Ciallella JR, Lipinski CA, Reaume AG | title=Drug Repositioning | chapter=Phenotypic Screening | publisher=CRC Press | publication-place=Boca Raton | series = Frontiers in Neurotherapeutics | date=14 July 2017 | isbn=978-1-315-37366-9 | doi=10.4324/9781315373669-7 | pages=121–145 | url=https://www.researchgate.net/publication/333583200}}</ref> It is currently undergoing research trials for potential application in treating Parkinson's disease and sleep disorders.<ref name="Businesswire2016">{{cite web|title=Melior Discovery Announces Spinout of Melior Pharmaceuticals II, LLC.|date=10 May 2016|url=https://www.businesswire.com/news/home/20160510005485/en/Melior-Discovery-Announces-Spinout-Melior-Pharmaceuticals-II}}</ref><ref name="AdisInsight">{{cite web | title=MLR-1017 - Melior Pharmaceuticals | website=AdisInsight | date=28 February 2023 | url=https://adisinsight.springer.com/drugs/800043871 | access-date=16 September 2024}}</ref> It is taken by mouth.
<!-- Side effects, mechanism of action, and chemistry --> The drug is a selective dopamine reuptake inhibitor (DRI).<ref name="NepalDasReith2023" /><ref name="NguyenChengLee2024" /><ref name="AggarwalChengSalvino2021" /><ref name="ErdöKissRosdy1981" /> It is an unusual and unique DRI, acting as a negative allosteric modulator and non-competitive inhibitor of the dopamine transporter (DAT).<ref name="NepalDasReith2023" /><ref name="NguyenChengLee2024" /><ref name="AggarwalChengSalvino2021" /> Chemically, mesocarb contains amphetamine within its structure but has been modified and extended at the amine with a sydnone imine-containing moiety.<ref name="PubChem">{{cite web | title=Mesocarb | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/9551611 | access-date=16 September 2024}}</ref><ref name="Elks2014" /><ref name="IndexNominum2000" />
<!-- History, society, and culture --> Mesocarb was first described by 1971.<ref name="Elks2014" /><ref name="AnokhinaZabrodinSvirinovskiĭ1974" /><ref name="PolgárVereczkeyCzira1978" /><ref name="ErdöKissRosdy1981" /> It was used as a pharmaceutical drug until 2008.<ref name="GlobeNewswire2021">{{cite press release | author = Adhera Therapeutics | title=Adhera Therapeutics Signs Letter of Intent with Melior Pharmaceuticals II to Acquire a New Class of Drug for Parkinson's Disease | website=GlobeNewswire News Room | date=7 June 2021 | url=https://www.globenewswire.com/news-release/2021/06/07/2242766/0/en/Adhera-Therapeutics-Signs-Letter-of-Intent-with-Melior-Pharmaceuticals-II-to-Acquire-a-New-Class-of-Drug-for-Parkinson-s-Disease.html | access-date=25 September 2024 | quote=Armesocarb is the active pharmaceutical ingredient (API) of the racemic mixture mesocarb, a highly selective dopamine reuptake inhibitor first approved in the former Soviet Union in 1971 and marketed for select psychiatric and central nervous system (CNS) indications until 2008. At that time, which coincided with the Great Recession, the Russian manufacturer discontinued operations for business reasons unrelated to the compound itself.}}</ref> In 2021, its nature as a DAT allosteric modulator was reported.<ref name="NepalDasReith2023" /><ref name="NguyenChengLee2024" /><ref name="AggarwalChengSalvino2021" /> As of February 2023, mesocarb was in phase 1 clinical trials for Parkinson's disease.<ref name="AdisInsight" /> The active enantiomer, armesocarb, is also being developed.<ref name="AdisInsight-Armesocarb" />
==Medical uses== Mesocarb was originally developed in the Soviet Union in the 1970s<ref name="GB1262830" /><ref>{{cite journal | vauthors = Anokhina IP, Zabrodin GD, Svirinovskiĭ I | title = [Characteristics of the central action of sidnocarb] | language = ru | journal = Zhurnal Nevropatologii I Psikhiatrii imeni S.S. Korsakova | volume = 74 | issue = 4 | pages = 594–602 | year = 1974 | pmid = 4825943 | trans-title = Characteristics of the central action of sidnocarb }}</ref> for a variety of indications including asthenia, apathy, adynamia, and some clinical aspects of depression and schizophrenia.<ref name="RudenkoAltshuler1979">{{cite journal | vauthors = Rudenko GM, Altshuler RA | title = Peculiarities of clinical activity and pharmacokinetics of sydnocarb (sydnocarbum), an original psychostimulant | journal = Agressologie | volume = 20 | issue = D | pages = 265–270 | year = 1979 | pmid = 45391 }}</ref><ref name="WitkinSavtchenkoMashkovsky1999">{{cite journal | vauthors = Witkin JM, Savtchenko N, Mashkovsky M, Beekman M, Munzar P, Gasior M, Goldberg SR, Ungard JT, Kim J, Shippenberg T, Chefer V | title = Behavioral, toxic, and neurochemical effects of sydnocarb, a novel psychomotor stimulant: comparisons with methamphetamine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 288 | issue = 3 | pages = 1298–1310 | date = March 1999 | doi = 10.1016/S0022-3565(24)38086-3 | pmid = 10027871 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10027871 | url-access = subscription }}</ref> Mesocarb was used for counteracting the sedative effects of benzodiazepines,<ref name="ValuevaTozhanova1982">{{cite journal | vauthors = Valueva LN, Tozhanova NM | title = [Sidnocarb correction of the adverse effects of benzodiazepine tranquilizers] | language = ru | journal = Zhurnal Nevropatologii I Psikhiatrii imeni S.S. Korsakova | volume = 82 | issue = 8 | pages = 92–97 | year = 1982 | pmid = 6127851 | trans-title = Sidnocarb correction of the adverse effects of benzodiazepine tranquilizers }}</ref> increasing workload capacity and cardiovascular function,<ref name="VinarKleinPotter1991">{{cite journal | vauthors = Vinar O, Klein DF, Potter WZ, Gause EM | title = A survey of psychotropic medications not available in the United States | journal = Neuropsychopharmacology | volume = 5 | issue = 4 | pages = 201–217 | date = December 1991 | pmid = 1804161 }}</ref> treatment of attention deficit hyperactivity disorder (ADHD) in children,<ref name="TurovaMisionzhnikErmolina1988">{{cite journal | vauthors = Turova NF, Misionzhnik EI, Ermolina LA, Aziavchik AV, Krasov VA | title = [Excretion of monoamines, their precursors and metabolites in the hyperactivity syndrome in mentally defective children] | language = ru | journal = Voprosy Meditsinskoi Khimii | volume = 34 | issue = 1 | pages = 47–50 | year = 1988 | pmid = 3369126 | trans-title = Excretion of monoamines, their precursors and metabolites in the hyperactivity syndrome in mentally defective children }}</ref><ref name="Krasov1988">{{cite journal | vauthors = Krasov VA | title = [Sidnocarb treatment of young schoolchildren with the hyperdynamic syndrome] | language = ru | journal = Zhurnal Nevropatologii I Psikhiatrii imeni S.S. Korsakova | volume = 88 | issue = 8 | pages = 97–101 | year = 1988 | pmid = 3195293 | trans-title = Sidnocarb treatment of young schoolchildren with the hyperdynamic syndrome }}</ref> as a nootropic,<ref name="GanievKharlamovRaevskiĭ1987">{{cite journal | vauthors = Ganiev MM, Kharlamov AN, Raevskiĭ KS, Guseĭnov DI | title = [Effect of sidnocarb on learning and memory] | language = ru | journal = Biulleten' Eksperimental'noi Biologii I Meditsiny | volume = 104 | issue = 10 | pages = 453–454 | date = October 1987 | pmid = 3676468 | trans-title = Effect of sidnocarb on learning and memory }}</ref> and as a drug to enhance resistance to extremely cold temperatures.<ref name="BarerLakotaOstrovskaia1988">{{cite journal | vauthors = Barer AS, Lakota NG, Ostrovskaia GZ, Shashkov VS | title = [Pharmacologic correction of the effect of cold on man] | language = ru | journal = Kosmicheskaia Biologiia I Aviakosmicheskaia Meditsina | volume = 22 | issue = 6 | pages = 66–73 | date = Nov–Dec 1988 | pmid = 2906380 | trans-title = Pharmacologic correction of the effect of cold on man }}</ref><ref name="LevinaBadyshtovGan'shina2006">{{cite journal | vauthors = Levina MN, Badyshtov BA, Gan'shina TS | title = [Thermoprotector properties of a combination of sydnocarb with ladasten] | language = ru | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 69 | issue = 1 | pages = 71–73 | year = 2006 | pmid = 16579065 | trans-title = Thermoprotector properties of a combination of sydnocarb with ladasten }}</ref> It has also been reported to have antidepressant and anticonvulsant properties.<ref name="KawaseSakagamiMotohashi2007" />
===Available forms=== Mesocarb was sold in Russia as 5{{nbsp}}mg oral tablets under the brand name Sydnocarb.{{Citation needed|date=September 2024}}
==Pharmacology== ===Pharmacodynamics=== Mesocarb has been found to act as a selective dopamine reuptake inhibitor (DRI) by blocking the actions of the dopamine transporter (DAT),<ref name="ErdöKissRosdy1981" /><ref name="GrunerMathiasenFlood2011">{{cite journal | vauthors = Gruner JA, Mathiasen JR, Flood DG, Gasior M | title = Characterization of pharmacological and wake-promoting properties of the dopaminergic stimulant sydnocarb in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 337 | issue = 2 | pages = 380–390 | date = May 2011 | pmid = 21300706 | doi = 10.1124/jpet.111.178947 | s2cid = 9985668 }}</ref> and lacks the dopamine release characteristic of stimulants such as dextroamphetamine.<ref>{{cite journal | vauthors = Afanas'ev II, Anderzhanova EA, Kudrin VS, Rayevsky KS | title = Effects of amphetamine and sydnocarb on dopamine release and free radical generation in rat striatum | journal = Pharmacology, Biochemistry, and Behavior | volume = 69 | issue = 3–4 | pages = 653–658 | year = 2001 | pmid = 11509228 | doi = 10.1016/S0091-3057(01)00574-3 | s2cid = 32739707 }}</ref><ref name="AnderzhanovaAfanas'evKudrin2000">{{cite journal | vauthors = Anderzhanova EA, Afanas'ev II, Kudrin VS, Rayevsky KS | title = Effect of d-amphetamine and sydnocarb on the extracellular level of dopamine, 3,4-dihydroxyphenylacetic acid, and hydroxyl radicals generation in rat striatum | journal = Annals of the New York Academy of Sciences | volume = 914 | issue = 1 | pages = 137–145 | date = September 2000 | pmid = 11085316 | doi = 10.1111/j.1749-6632.2000.tb05191.x | s2cid = 12326076 | bibcode = 2000NYASA.914..137A }}</ref><ref name="GainetdinovSotnikovaGrekhova1997">{{cite journal | vauthors = Gainetdinov RR, Sotnikova TD, Grekhova TV, Rayevsky KS | title = Effects of a psychostimulant drug sydnocarb on rat brain dopaminergic transmission in vivo | journal = European Journal of Pharmacology | volume = 340 | issue = 1 | pages = 53–58 | date = December 1997 | pmid = 9527506 | doi = 10.1016/S0014-2999(97)01407-6 }}</ref> It was the most selective DAT inhibitor amongst an array of other DAT inhibitors to which it was compared and, in 2017, was reported as the most selective DAT inhibitor described to date.<ref name="GrunerMathiasenFlood2011"/><ref name="Macolino-KaneCiallellaLipinski2017" />
The affinities (K<sub>i</sub>) of mesocarb at the human monoamine transporters ''in vitro'' have been reported to be 8.3{{nbsp}}nM for the dopamine transporter (DAT), 1,500{{nbs}}nM for the norepinephrine transporter (NET) (181-fold lower than for the DAT), and >10,000{{nbsp}}nM for the serotonin transporter (SERT) (>1,205-fold lower than for the DAT).<ref name="Macolino-KaneCiallellaLipinski2017" /> The inhibitory potencies ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}}) of mesocarb at the human monoamine transporters ''in vitro'' have been reported to be 0.49 ± 0.14{{nbsp}}μM at the DAT, 34.9 ± 14.08{{nbsp}}μM at the NET (71-fold lower than for the DAT), and 494.9 ± 17.00{{nbsp}}μM at the SERT (1,010-fold lower than for the DAT).<ref name="AggarwalChengSalvino2021" />
In 2021, it was discovered that mesocarb is not a conventional DRI but acts as a DAT allosteric modulator or non-competitive inhibitor.<ref name="NepalDasReith2023">{{cite journal | vauthors = Nepal B, Das S, Reith ME, Kortagere S | title = Overview of the structure and function of the dopamine transporter and its protein interactions | journal = Front Physiol | volume = 14 | issue = | article-number = 1150355 | date = 2023 | pmid = 36935752 | pmc = 10020207 | doi = 10.3389/fphys.2023.1150355 | doi-access = free | url = }}</ref><ref name="NguyenChengLee2024">{{cite journal | vauthors = Nguyen H, Cheng MH, Lee JY, Aggarwal S, Mortensen OV, Bahar I | title = Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments | journal = Curr Res Physiol | volume = 7 | issue = | article-number = 100125 | date = 2024 | pmid = 38836245 | pmc = 11148570 | doi = 10.1016/j.crphys.2024.100125 | url = }}</ref><ref name="AggarwalChengSalvino2021">{{cite journal | vauthors = Aggarwal S, Cheng MH, Salvino JM, Bahar I, Mortensen OV | title = Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter | journal = Biomedicines | volume = 9 | issue = 6 | date = June 2021 | page = 634 | pmid = 34199621 | pmc = 8227285 | doi = 10.3390/biomedicines9060634 | doi-access = free | url = }}</ref> In accordance with its nature as an atypical DAT blocker, the drug has atypical effects relative to conventional DRIs.<ref name="NepalDasReith2023" /><ref name="NguyenChengLee2024" /><ref name="AggarwalChengSalvino2021" /><ref name="Macolino-KaneCiallellaLipinski2017" /> As an example, it shows greater antiparkinsonian activity relative to other DRIs in animals.<ref name="Macolino-KaneCiallellaLipinski2017" />
Similarly to other DRIs, mesocarb has been found to possess wakefulness-promoting effects.<ref name="Macolino-KaneCiallellaLipinski2017" />
===Pharmacokinetics=== Hydroxylated metabolites can be detected in urine for up to 10{{nbsp}}days after consumption.<ref name="ShpakAppolonovaSemenov2005">{{cite journal | vauthors = Shpak AV, Appolonova SA, Semenov VA | title = Validation of liquid chromatography-electrospray ionization ion trap mass spectrometry method for the determination of mesocarb in human plasma and urine | journal = Journal of Chromatographic Science | volume = 43 | issue = 1 | pages = 11–21 | date = January 2005 | pmid = 15808002 | doi = 10.1093/chromsci/43.1.11 | doi-access = free }}</ref>
Mesocarb had erroneously been referred to as a prodrug of amphetamine.<ref name="DettmeyerVerhoff2013">{{cite book| vauthors = Dettmeyer R, Verhoff MA, Schütz HF |title=Forensic Medicine: Fundamentals and Perspectives|url=https://books.google.com/books?id=yHHABAAAQBAJ&pg=PA519|date=9 October 2013|publisher=Springer Science & Business Media|isbn=978-3-642-38818-7|pages=519–}}</ref> However, this was based on older literature that relied on gas chromatography as an analytical method. Subsequently, with the advent of mass spectroscopy, it has been shown that presence of amphetamine in prior studies was an artifact of the gas chromatography method.<ref>{{cite journal | vauthors = Appolonova SA, Shpak AV, Semenov VA | title = Liquid chromatography-electrospray ionization ion trap mass spectrometry for analysis of mesocarb and its metabolites in human urine | journal = Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences | volume = 800 | issue = 1–2 | pages = 281–289 | date = February 2004 | pmid = 14698267 | doi = 10.1016/j.jchromb.2003.10.071 }}</ref> More recent studies using mass spectroscopy show that negligible levels of amphetamine are released from mesocarb metabolism.<ref name="ShpakAppolonovaSemenov2005" />
==Chemistry== Mesocarb, also known as 3-(β-phenylisopropyl)-''N''-phenylcarbamoylsydnonimine, is a substituted phenethylamine and amphetamine and a mesoionic sydnone imine.<ref name="PubChem" /><ref name="Elks2014" /><ref name="IndexNominum2000" /> It has the amphetamine backbone present, except that the ''R''<sub>N</sub> has a complicated imine side chain present.<ref name="PubChem" /><ref name="Elks2014" /><ref name="IndexNominum2000" />
Whereas mesocarb (MLR-1017) is a racemic mixture, the enantiopure levorotatory or (''R'')-enantiomer is known as armesocarb (MLR-1019).<ref name="GlobeNewswire2021" /> Armesocarb is described as the active enantiomer of mesocarb, whereas the (''S'')- or <small>D</small>-enantiomer is said to be virtually inactive.<ref name="Macolino-KaneCiallellaLipinski2017" /><ref name="GlobeNewswire2021" /><ref name="Al'tschuler2005">{{cite journal | last=Al'tshuler | first=R. A. | title=Comparative Molecular Model Estimation of the Affinity of Phenylethylamines to the Binding Sites of Membrane Transporters | journal=Pharmaceutical Chemistry Journal | volume=39 | issue=4 | date=2005 | issn=0091-150X | doi=10.1007/s11094-005-0110-3 | pages=169–175}}</ref>
It is structurally related to feprosidnine (Sydnophen; 3-(α-methylphenylethyl)sydnone imine).<ref name="KawaseSakagamiMotohashi2007">{{cite book | vauthors = Kawase M, Sakagami H, Motohashi N | title=Bioactive Heterocycles VII | chapter=The Chemistry of Bioactive Mesoionic Heterocycles | series=Topics in Heterocyclic Chemistry | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | volume=16 | date=2007 | isbn=978-3-642-00335-6 | doi=10.1007/7081_2007_096 | pages=135–152 | quote=Mesocarb (sydnocarb) (13) and Feprosidnine (sydnofen) (14) are stimulants developed in Russia in the 1970s. Mesocarb is sold as a drug in Russia. However, it is almost unknown in Western countries and is not used in medicine. It has been shown to act as a dopamine reuptake inhibitor, antidepressant, and anticonvulsant [7, 8].}}</ref>
===Synthesis=== class=skin-invert-image|500px|thumb|centre|Patents:<ref name="GB1262830">{{cite patent | inventor = Mashkovskii ME, Yashunskii VG, Altshuler RA, Kholodov LE, Avrutskii GY, Aleksandrovskii YA, Shmulevich AB | country = DE | number = 2028880 | assign = Ordzhonikidze, S., All-Union Scientific-Research Chemical-Pharmaceutical Institute | gdate = 8 March 1979 | title = N-(Phenylcarbamoyl)-3-(1-phenyl-2-propyl)sydnone imine }}</ref><ref>{{cite patent | url = https://patents.google.com/patent/GB1262830A/ | inventor = Mashkovsky MD, Yashunsky YG, Altshuller RA, Knolodov LE, Avrutsky GY, Alexandrovsky JA, Smulevich AB | country = GB | number = 1262830 | assign = Vni Khim Farmatsevtichesky II | pubdate = 9 February 1972 | title = Novel sydnonimine derivative }}</ref>
Feprosidnine (Sydnophen) is converted from the hydrochloride salt ('''1''') into the freebase amine ('''2'''). This is then treated with phenylisocyanate ('''3''').
==History== Mesocarb was first described in the scientific literature by 1971.<ref name="Elks2014" /><ref name="AnokhinaZabrodinSvirinovskiĭ1974">{{cite journal | vauthors = Anokhina IP, Zabrodin GD, Svirinovskiĭ IE | title = Osobennosti mekhanizma tsentral'nogo deĭstviia sidnokarba | trans-title = Characteristics of the central action of sidnocarb | language = Russian | journal = Zh Nevropatol Psikhiatr Im S S Korsakova | volume = 74 | issue = 4 | pages = 594–602 | date = 1974 | pmid = 4825943 | doi = | url = }}</ref><ref name="PolgárVereczkeyCzira1978">{{cite journal | vauthors = Polgár M, Vereczkey L, Czira G, Tamás J, Szporny L | title = Sydnocarb metabolizmusának vizsgálata pathányban | trans-title = Synocarb metabolism in rats | language = Hungarian | journal = Acta Pharm Hung | volume = 48 | issue = Suppl | pages = 23–24 | date = 1978 | pmid = 749521 | doi = | url = }}</ref><ref name="ErdöKissRosdy1981">{{cite journal | vauthors = Erdö SL, Kiss B, Rosdy B | title = Inhibition of dopamine uptake by a new psychostimulant mesocarb (Sydnocarb) | journal = Pol J Pharmacol Pharm | volume = 33 | issue = 2 | pages = 141–147 | date = 1981 | pmid = 7312716 | doi = | url = }}</ref> It is said to have been used as a pharmaceutical drug from 1971 until 2008.<ref name="GlobeNewswire2021" /> It was said to have been discontinued by its manufacturer in 2008 for business reasons unrelated to the drug itself.<ref name="GlobeNewswire2021" />
==Society and culture== ===Names=== ''Mesocarb'' is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}.<ref name="PubChem" /> It is also known by the synonym ''fensidnimine'' as well as by the brand names ''Sydnocarb'' and ''Synocarb''.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="PubChem" /><ref name="CASCommonChemistry">{{cite web | title= Mesocarb | id = CAS Registry Number 34262-84-5 | work=CAS Common Chemistry | publisher = American Chemical Society | date=16 September 2024 | url=https://commonchemistry.cas.org/detail?cas_rn=34262-84-5 | access-date=16 September 2024}}</ref> The drug is additionally known by its developmental code name ''MLR-1017'' (for Parkinson's disease).<ref name="AdisInsight" />
===Status=== Mesocarb is almost unknown in the western world and is neither used in medicine nor studied scientifically to any great extent outside of Russia and other countries in the former Soviet Union. It has however been added to the list of drugs under international control and is a scheduled substance in most countries, despite its multiple therapeutic applications and reported lack of significant abuse potential.<ref>{{cite journal |vauthors=Rudenko GM, Altshuler RA |title=[Experimental and clinical study of Sydnocarb] |language=ru |journal=Hung Pharmacotherapy |volume=124 |pages=150–154 |year=1978}}</ref>
==Research== ===Parkinson's disease=== Mesocarb, has been under development for the treatment of Parkinson's disease since 2016.<ref name="Businesswire2016" /><ref name="AdisInsight" /> As of February 2023, it is in phase 1 clinical trials for this indication.<ref name="AdisInsight" /> However, no recent development has been reported.<ref name="AdisInsight" /> Mesocarb's active enantiomer armesocarb is also under development.<ref name="AdisInsight-Armesocarb">{{cite web | title=Melior Pharmaceuticals | website=AdisInsight | date=28 April 2023 | url=https://adisinsight.springer.com/drugs/800034792 | access-date=26 September 2024}}</ref>
==See also== * List of Russian drugs * List of investigational Parkinson's disease drugs
==References== {{Reflist}}
{{Stimulants}} {{Monoamine reuptake inhibitors}} {{Phenethylamines}}
Category:Antidepressants Category:Antiparkinsonian agents Category:Dopamine reuptake inhibitors Category:Drugs in the Soviet Union Category:Experimental drugs Category:Imines Category:Oxadiazoles Category:Russian drugs Category:Stimulants Category:Substituted amphetamines Category:Ureas Category:Wakefulness-promoting agents Category:Withdrawn drugs