Phenylpiracetam

{{Short description|Chemical compound}} {{Multiple issues|{{Medref|date=September 2014}}}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = verified | Watchedfields = verified | INN = Fonturacetam | verifiedrevid = 447920554 | image = Phenylpiracetam.svg | image_class = skin-invert-image | width = 125px | image2 = Phenylpiracetam.png | image_class2 = bg-transparent | width2 = 125px

| tradename = Phenotropil, Carphedon, Actitropil, others | pregnancy_category = Unknown | legal_AU = S4 | legal_US = Unapproved drug; use in dietary supplements, food, or medicine is unlawful. | legal_status = RU: Rx-only | routes_of_administration = By mouth<ref name="MalykhSadaie2010" /><ref name="Phenylpiracetam-Leaflet" /> | bioavailability = ~100%<ref name="MalykhSadaie2010" /><ref name="Phenylpiracetam-Leaflet" /> | protein_bound = | metabolism = Not metabolized<ref name="Phenylpiracetam-Leaflet" /> | metabolites = | elimination_half-life = 3–5 hours<ref name="MalykhSadaie2010" /><ref name="Phenylpiracetam-Leaflet" /> | onset = <1{{nbsp}}hour<ref name="Phenylpiracetam-Leaflet" /><ref name="MalykhSadaie2010" /> | excretion = Urine: ~40%<ref name="Phenylpiracetam-Leaflet" /> Bile, sweat: ~60%<ref name="Phenylpiracetam-Leaflet" />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 77472-70-9 | ATC_prefix = None | PubChem = 132441 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 116950 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = 99QW5JU66Y | synonyms = Fonturacetam; Phenotropil; Fenotropil; 4-Phenylpiracetam; PP<ref name="GromovaTorshin2024" />

| IUPAC_name = (''R'',''S'')-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide | C = 12 | H = 14 | N = 2 | O = 2 | SMILES = C1=CC=CC=C1C2CN(C(C2)=O)CC(=O)N | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C12H14N2O2/c13-11(15)8-14-7-10(6-12(14)16)9-4-2-1-3-5-9/h1-5,10H,6-8H2,(H2,13,15) | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = LYONXVJRBWWGQO-UHFFFAOYSA-N | chirality = Racemic mixture

| boiling_point = 486.4 }}  '''Phenylpiracetam''', also known as '''fonturacetam''' ({{Abbrlink|INN|International nonproprietary name}}) and sold under the brand names '''Phenotropil''', '''Actitropil''', and '''Carphedon''' among others, is a stimulant and nootropic medication used in Russia and certain other Eastern European countries in the treatment of cerebrovascular deficiency, depression, apathy, attention, and memory problems, among other indications.<ref name="MalykhSadaie2010">{{cite journal | vauthors = Malykh AG, Sadaie MR | title = Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders | journal = Drugs | volume = 70 | issue = 3 | pages = 287–312 | date = February 2010 | pmid = 20166767 | doi = 10.2165/11319230-000000000-00000 | url = }}</ref><ref name="VeinbergVaversOrlova2015">{{cite journal | vauthors = Veinberg G, Vavers E, Orlova N, Kuznecovs J, Domracheva I, Vorona M, Zvejniece L, Dambrova M | title=Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile | journal=Chemistry of Heterocyclic Compounds | volume=51 | issue=7 | date=2015 | issn=0009-3122 | doi=10.1007/s10593-015-1747-9 | pages=601–606 | quote = Phenylpiracetam was originally designed as a nootropic drug for the sustenance and improvement of the physical condition and cognition abilities of Soviet space crews.2 Later, especially during the last decade, phenylpiracetam was introduced into general clinical practice in Russia and in some Eastern European countries. The possible target receptors and mechanisms for the acute activity of this drug remained unclear, until very recently it was found that (R)-phenylpiracetam (5) (MRZ-9547) is a selective dopamine transporter inhibitor that moderately stimulates striatal dopamine release.19}}</ref><ref name="GromovaTorshin2024">{{cite journal | vauthors = Gromova OA, Torshin IY | title = Farmakologičeskie èffekty fonturacetama (Aktitropil) i perspektivy ego kliničeskogo primenenija | trans-title = Pharmacological effects of fonturacetam (Actitropil) and prospects for its clinical use | language = Russian | journal = Zh Nevrol Psikhiatr Im S S Korsakova | trans-journal = S.S. Korsakov Journal of Neurology and Psychiatry | volume = 124 | issue = 8 | pages = 21–31 | date = 2024 | pmid = 39269293 | doi = 10.17116/jnevro202412408121 | url = }}</ref><ref name="Phenylpiracetam-Leaflet">{{Cite web| title=Fonturacetam | url=https://russianmeds.com/pdf/fonturacetam.pdf | archive-url=https://web.archive.org/web/20221126092520/https://russianmeds.com/pdf/fonturacetam.pdf | archive-date=2022-11-26}}</ref> It is also used in Russian cosmonauts to improve physical, mental, and cognitive abilities.<ref name="MalykhSadaie2010" /><ref name="GromovaTorshin2024" /> The drug is taken by mouth.<ref name="MalykhSadaie2010" />

Side effects of phenylpiracetam include sleep disturbances among others.<ref name="MalykhSadaie2010" /> The mechanism of action of phenylpiracetam was originally unknown.<ref name="MalykhSadaie2010" /><ref name="VeinbergVaversOrlova2015" /><ref name="Voronina2023">{{cite journal | vauthors = Voronina TA | title=Cognitive Impairment and Nootropic Drugs: Mechanism of Action and Spectrum of Effects | journal=Neurochemical Journal | publisher=Pleiades Publishing Ltd | volume=17 | issue=2 | year=2023 | issn=1819-7124 | doi=10.1134/s1819712423020198 | doi-access=free | pages=180–188 | quote=Phenylpiracetam, a phenyl analogue of piracetam (trade names: phenotropil, carphedon, and phenylpiracetam), was developed at the Institute of Biomedical Problems as a new generation psychostimulant that can increase the mental and physical performance of astronauts at various stages of space flights. It was experimentally established that phenylpiracetam improves learning and memory, has an antiamnesic effect, activates operant behavior, has anxiolytic, antiasthenic, and anticonvulsant effects, weakens the sedative effect of benzodiazepines, increases resistance to cold, and improves sleep [29–31]. In a model of cerebral ischemia, phenylpiracetam improves cognitive functions, reduces manifestations of neurological deficit, and is superior in effectiveness to piracetam [32, 33]. It has been shown that phenylpiracetam does not bind to GABA-A, GABA-B and dopamine receptors, or 5-HT2 serotonin receptor, but is a synaptic transmission modulator and binds to α4β2 nicotinic acetylcholine receptors in the cerebral cortex (IC50 = 5.86 μm) [34, 35].}}</ref> However, it was discovered that (''R'')-phenylpiracetam is a selective atypical dopamine reuptake inhibitor in 2014.<ref name="VeinbergVaversOrlova2015" /><ref name="SommerDanyszRuss2014">{{cite journal | vauthors = Sommer S, Danysz W, Russ H, Valastro B, Flik G, Hauber W | title = The dopamine reuptake inhibitor MRZ-9547 increases progressive ratio responding in rats | journal = The International Journal of Neuropsychopharmacology | volume = 17 | issue = 12 | pages = 2045–2056 | date = December 2014 | pmid = 24964269 | doi = 10.1017/S1461145714000996 | quote = Here, we tested the effects of MRZ-9547 [...], and its l-enantiomer MRZ-9546 on effort-related decision making in rats. The racemic form of these compounds referred to as phenotropil has been shown to stimulate motor activity in rats (Zvejniece et al., 2011) and enhance physical capacity and cognition in humans (Malykh and Sadaie, 2010). [...] MRZ-9547 turned out to be a DAT inhibitor as shown by displacement of binding of [125I] RTI-55 (IC50 = 4.82 ± 0.05 μM, n=3) to human recombinant DAT expressed in CHO-K1 cells and inhibition of DA uptake (IC50 = 14.5 ± 1.6 μM, n=2) in functional assays in the same cells. It inhibited norepinephrine transporter (NET) with an IC50 of 182 μM (one experiment in duplicate). The potencies for the l-enantiomer MRZ-9546 were as follows: DAT binding (Ki = 34.8 ± 14.8 μM, n=3), DAT function (IC50 = 65.5 ± 8.3 μM, n=2) and NET function (IC50 = 667 μM, one experiment performed in duplicate). }}</ref> In addition, phenylpiracetam interacts with certain nicotinic acetylcholine receptors.<ref name="Voronina2023" /> Chemically, phenylpiracetam is a racetam and phenethylamine and is structurally related to piracetam.<ref name="MalykhSadaie2010" /><ref name="GouliaevSenning1994">{{cite journal | vauthors = Gouliaev AH, Senning A | title = Piracetam and other structurally related nootropics | journal = Brain Res Brain Res Rev | volume = 19 | issue = 2 | pages = 180–222 | date = May 1994 | pmid = 8061686 | doi = 10.1016/0165-0173(94)90011-6 | url = | quote = As mentioned above, no commonly accepted mechanism for the racetam nootropics has yet been established, They do not seem to act on any well characterised receptor site with the exception of nefiracetam which has high affinity for GABA, receptors (see Table 1). [...] Receptor: GABAA. Receptor ligand: [3H]muscimolA. Compound: nefiracetam. IC50: 8.5 nMB. Refs.: 222. [...] From Table 1 it is, however, evident that the piracetam-like nootropics do not exhibit high affinity for any of the receptor types tested so far (except for nefiracetam, which shows some activity at GABAA receptors)}}</ref>

Phenylpiracetam was first described in 1983 by Bobkov Iu, et al.<ref name="BobkovMorozovGlozman1983" /> It was approved for medical use in Russia in 2003.<ref name="MalykhSadaie2010" /> Development of (''R'')-phenylpiracetam (code name MRZ-9547) in the West as a potential treatment for fatigue related to Parkinson's disease began by 2014.<ref name="AdisInsight-MRZ-9547" /><ref name="SommerDanyszRuss2014" /> In addition to its medical use, phenylpiracetam is sold online as a nootropic.<ref name="Aipsin">{{cite web | title=Фенилпирацетам (Phenylpiracetam) | website=АИПСИН | url=https://aipsin.com/newsubstance/674/ | language=ru | access-date=1 January 2026}}</ref>

==Medical uses== Phenylpiracetam is used in the treatment of a variety of different medical conditions.<ref name="MalykhSadaie2010" /><ref name="GromovaTorshin2024" /><ref name="Phenylpiracetam-Leaflet" /> It is specifically approved in Russia for treatment of cerebrovascular deficiency, depression, apathy, attention deficits, and memory decline.<ref name="MalykhSadaie2010" /><ref name="GromovaTorshin2024" /><ref name="Phenylpiracetam-Leaflet" /> It is used to improve symptoms following encephalopathy, brain injury, and glioma surgery.<ref name="MalykhSadaie2010" /><ref name="GromovaTorshin2024" /><ref name="Phenylpiracetam-Leaflet" /> The drug has been reported to improve symptoms of depression, anxiety, asthenia, and fatigue, as well as to improve cognitive performance and memory.<ref name="MalykhSadaie2010" /><ref name="GromovaTorshin2024" /><ref name="Phenylpiracetam-Leaflet" /> It also has anticonvulsant effects and has been used as an add-on therapy in epilepsy.<ref name="MalykhSadaie2010" /><ref name="GromovaTorshin2024" />

Phenylpiracetam is typically prescribed as a general stimulant or to increase tolerance to extreme temperatures and stress.<ref name="KimParkMyung1999">{{cite journal |vauthors=Kim S, Park JH, Myung SW, Lho DS |date=November 1999 |title=Determination of carphedon in human urine by solid-phase microextraction using capillary gas chromatography with nitrogen-phosphorus detection |journal=The Analyst |volume=124 |issue=11 |pages=1559–1562 |bibcode=1999Ana...124.1559K |doi=10.1039/a906027h |pmid=10746314}}</ref>

Clinical use of phenylpiracetam has shown to be more potent than piracetam and is used for a wider-range of indications.<ref name="MalykhSadaie2010" />

A few small clinical studies have shown possible links between prescription of phenylpiracetam and improvement in a number of encephalopathic conditions, including lesions of cerebral blood pathways, traumatic brain injury and certain types of glioma.<ref name="SavchenkoZakharovaStepanov2005">{{cite journal | vauthors = Savchenko AI, Zakharova NS, Stepanov IN | title = [The phenotropil treatment of the consequences of brain organic lesions] | journal = Zhurnal Nevrologii I Psikhiatrii imeni S.S. Korsakova | volume = 105 | issue = 12 | pages = 22–26 | year = 2005 | pmid = 16447562 }}</ref>

Clinical trials were conducted at the Serbsky State Scientific Center for Social and Forensic Psychiatry. The Serbsky Center, Moscow Institute of Psychiatry, and Russian Center of Vegetative Pathology are reported to have confirmed the effectiveness of phenylpiracetam describing the following effects: improvement of regional blood flow in ischemic regions of the brain, reduction of depressive and anxiety disorders, increase the resistance of brain tissue to hypoxia and toxic effects, improving concentration and mental activity, a psycho-activating effect, increase in the threshold of pain sensitivity, improvement in the quality of sleep, and an anticonvulsant action,<ref name="LybzikovaIaglovaKharlamova2008">{{cite journal | vauthors = Lybzikova GN, ((Iaglova Zh)), ((Kharlamova Iu)) | title = [The efficacy of phenotropil in the complex treatment of epilepsy] | language = Russian | journal = Zh Nevrol Psikhiatr Im S S Korsakova | volume = 108 | issue = 2 | pages = 69–70 | date = 2008 | pmid = 18646385 | doi = | url = }}</ref> though with the side effect of an anorexic effect in extended use.<ref name="KalinskiĭNazarov2007">{{cite journal | vauthors = Kalinskiĭ PP, Nazarov VV | title = [Use of phenotropil in the treatment of asthenic syndrome and autonomic disturbances in the acute period of mild cranial brain trauma] | language = Russian | journal = Zh Nevrol Psikhiatr Im S S Korsakova | volume = 107 | issue = 2 | pages = 61–63 | date = 2007 | pmid = 18689001 | doi = | url = }}</ref><ref name="GustovSmirnovKorshunova2006">{{cite journal | vauthors = Gustov AA, Smirnov AA, ((Korshunova Iu)), Andrianova EV | title = [Phenotropil in the treatment of vascular encephalopathy] | language = Russian | journal = Zh Nevrol Psikhiatr Im S S Korsakova | volume = 106 | issue = 3 | pages = 52–53 | date = 2006 | pmid = 16608112 | doi = | url = }}</ref>

===Available forms=== Phenylpiracetam is available in the form of 100{{nbsp}}mg oral tablets.<ref name="ValentaPharma-Phenotropil">{{cite web | title=Phenotropil® | website=АО «Валента Фарм» | url=https://www.valentapharm.com/eng/products/psychoneurology/phenotropil/ | language=ru | access-date=27 September 2024}}</ref><ref name="Phenylpiracetam-Leaflet" />

==Contraindications== Phenylpiracetam has a number of contraindications, such as individual intolerance.<ref name="Phenylpiracetam-Leaflet" />

==Side effects== Side effects of phenylpiracetam include insomnia or sleep disturbances, psychomotor agitation, flushing, a feeling of warmth, and increased blood pressure, among others.<ref name="MalykhSadaie2010" /><ref name="Phenylpiracetam-Leaflet" />

==Overdoses== Overdose has not been reported.<ref name="Phenylpiracetam-Leaflet" />

==Pharmacology== ===Pharmacodynamics=== Phenylpiracetam is a racetam and is described as a stimulant.<ref name="MalykhSadaie2010" /><ref name="VeinbergVaversOrlova2015" /><ref name="GromovaTorshin2024" /><ref name="Phenylpiracetam-Leaflet" /> Racetams have a variety of different pharmacological activities and have varying effects.<ref name="Molina-CarballoCheca-RosMuñoz-Hoyos2016">{{cite journal | vauthors = Molina-Carballo A, Checa-Ros A, Muñoz-Hoyos A | title = Treatments and compositions for attention deficit hyperactivity disorder: a patent review | journal = Expert Opin Ther Pat | volume = 26 | issue = 7 | pages = 799–814 | date = July 2016 | pmid = 27138211 | doi = 10.1080/13543776.2016.1182989 | url = | quote = The racetams have different activities [e.g., phenylpiracetam is a stimulant developed and marketed in Russia, piracetam is a nootropic, and levetiracetam is widely used as an anticonvulsant (Figure 17)].}}</ref><ref name="GualtieriManettiRomanelli2002">{{cite journal | vauthors = Gualtieri F, Manetti D, Romanelli MN, Ghelardini C | title = Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs | journal = Curr Pharm Des | volume = 8 | issue = 2 | pages = 125–138 | date = 2002 | pmid = 11812254 | doi = 10.2174/1381612023396582 | url = | quote = In general, piracetam-like nootropics show no affinity for the most important central receptors (Ki > 10 μM). A modest affinity for muscarinic receptors is shown by aniracetam (Ki = 4.4 μM [58]) and nebracetam (Ki = 6.3 μM [61]). Nefiracetam is the only one showing affinity in the nanomolar range (Ki = 8.5 nM on the GABAA receptor [58]). [...] Nefiracetam (chart (1)) is awaiting approval. It presents a variety of pharmacological actions as it is reported to activate the cholinergic, GABAergic and other monaminergic systems and to modulate N-type calcium channels [78-81].}}</ref><ref name="GouliaevSenning1994" /><ref name="NarahashiMoriguchiZhao2004">{{cite journal | vauthors = Narahashi T, Moriguchi S, Zhao X, Marszalec W, Yeh JZ | title = Mechanisms of action of cognitive enhancers on neuroreceptors | journal = Biol Pharm Bull | volume = 27 | issue = 11 | pages = 1701–1706 | date = November 2004 | pmid = 15516710 | doi = 10.1248/bpb.27.1701 | url = }}</ref><ref name="MalykhSadaie2010" /> For example, phenylpiracetam is a stimulant, piracetam is a nootropic, and levetiracetam is an anticonvulsant.<ref name="Molina-CarballoCheca-RosMuñoz-Hoyos2016" /> The mechanisms of action of most racetams, with some exceptions, are unknown.<ref name="GualtieriManettiRomanelli2002" /><ref name="GouliaevSenning1994" /><ref name="NarahashiMoriguchiZhao2004" />

Phenylpiracetam is a racemic mixture.<ref name="VeinbergVaversOrlova2015" /> (''R'')-Phenylpiracetam is the most active enantiomer and is much more potent in stimulating locomotor activity than (''S'')-phenylpiracetam, which is ineffective.<ref name="VeinbergVaversOrlova2015" /><ref name="ZvejnieceSvalbeVavers2017" /> However, (''S'')-phenylpiracetam retains some activity in most pharmacological tests.<ref name="VeinbergVaversOrlova2015" /> On the other hand, in one animal test, the passive avoidance test, (''S'')-phenylpiracetam appeared to be antagonistic of (''R'')-phenylpiracetam.<ref name="VeinbergVaversOrlova2015" />

====Dopamine reuptake inhibitor==== Experiments performed on Sprague-Dawley rats in a European patent for using phenylpiracetam to treat sleep disorders showed an increase in extracellular dopamine levels after administration. The patent asserts discovery of phenylpiracetam's action as a dopamine reuptake inhibitor<ref name="EP20140000021"/> as its basis.<ref name="KovalevAkhapkinaAbaimov2007">Kovalev, G. I., Akhapkina, V. I., Abaimov, D. A., & Firstova, Y. Y. (2007). Phenotropil as receptor modulator of synaptic neurotransmission. ''Nervnye Bolezni'', 4, 22–26. https://scholar.google.com/scholar?cluster=617408379890668058</ref>

{{Quote|The peculiarity of this invention compared to former treatment approaches for treating sleep disorders is the so far unknown therapeutic efficacy of (''R'')-phenylpiracetam, which is presumably based at least in part on the newly identified activity of (''R'')-phenylpiracetam as the dopamine re-uptake inhibitor}}

Both enantiomers of phenylpiracetam, (''R'')-phenylpiracetam and (''S'')-phenylpiracetam, have been described in peer-reviewed research as dopamine transporter (DAT) inhibitors in rodents, confirming the patent claim.<ref name="BoyleBettsLu2024">{{cite journal | vauthors = Boyle N, Betts S, Lu H | title=Monoaminergic Modulation of Learning and Cognitive Function in the Prefrontal Cortex | journal=Brain Sciences | publisher=MDPI AG | volume=14 | issue=9 | date=6 September 2024 | issn=2076-3425 | doi=10.3390/brainsci14090902 | doi-access=free | page=902 | pmid=39335398 | pmc=11429557 | quote = In recent years, the potential for cognitive enhancement through pharmacological modulation of dopamine levels in the PFC has garnered significant interest. The inverted-U functional effect of dopamine in the PFC suggests both insufficient and excessive DA levels impair cognitive performance, leading to the development of several compounds aimed at modulating dopamine levels to improve cognitive function. Many of these compounds, including CE-158, CE-123, and Sy-phenylpiracetam, work by inhibiting the dopamine transporter (DAT) to promote behavioral flexibility and cognitive enhancement in the PFC [99,100,101,102].}}</ref><ref name="ZvejnieceZvejnieceVideja2020">{{cite journal | vauthors = Zvejniece L, Zvejniece B, Videja M, Stelfa G, Vavers E, Grinberga S, Svalbe B, Dambrova M | title = Neuroprotective and anti-inflammatory activity of DAT inhibitor R-phenylpiracetam in experimental models of inflammation in male mice | journal = Inflammopharmacology | volume = 28 | issue = 5 | pages = 1283–1292 | date = October 2020 | pmid = 32279140 | doi = 10.1007/s10787-020-00705-7 | s2cid = 215731963 | url = https://zenodo.org/record/4600985 }}</ref><ref name="ZvejnieceSvalbeVavers2017">{{cite journal | vauthors = Zvejniece L, Svalbe B, Vavers E, Makrecka-Kuka M, Makarova E, Liepins V, Kalvinsh I, Liepinsh E, Dambrova M | title = S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity | journal = Pharmacology, Biochemistry, and Behavior | volume = 160 | pages = 21–29 | date = September 2017 | pmid = 28743458 | doi = 10.1016/j.pbb.2017.07.009 | s2cid = 13658335 }}</ref> Their actions at the norepinephrine transporter (NET) vary: (''R'')-phenylpiracetam acts as a dual norepinephrine–dopamine reuptake inhibitor (NDRI), with 11-fold lower affinity for the NET than for the DAT, whereas the (''S'')-enantiomer is selective for the DAT.<ref name="ZvejnieceSvalbeVavers2017"/> However, whereas (''R'')-phenylpiracetam stimulates locomotor activity, (''S'')-phenylpiracetam does not do so.<ref name="VeinbergVaversOrlova2015" /><ref name="ZvejnieceSvalbeVavers2017" /> This kind of variation in effects has also been seen with other dopamine reuptake inhibitors.<ref name="ReithBloughHong2015" /><ref name="HerseyBaconBailey2021" /><ref name="TandaHerseyHempel2021">{{cite journal | vauthors = Tanda G, Hersey M, Hempel B, Xi ZX, Newman AH | title = Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder | journal = Curr Opin Pharmacol | volume = 56 | issue = | pages = 13–21 | date = February 2021 | pmid = 32927246 | pmc = 8247144 | doi = 10.1016/j.coph.2020.07.007 | url = }}</ref><ref name="JordanCaoNewman2019">{{cite journal | vauthors = Jordan CJ, Cao J, Newman AH, Xi ZX | title = Progress in agonist therapy for substance use disorders: Lessons learned from methadone and buprenorphine | journal = Neuropharmacology | volume = 158 | issue = | article-number = 107609 | date = November 2019 | pmid = 31009632 | pmc = 6745247 | doi = 10.1016/j.neuropharm.2019.04.015 | url = }}</ref>

Other atypical dopamine reuptake inhibitors include modafinil,<ref name="ReithBloughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug Alcohol Depend | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 | url = }}</ref><ref name="HerseyBaconBailey2021">{{cite journal | vauthors = Hersey M, Bacon AK, Bailey LG, Coggiano MA, Newman AH, Leggio L, Tanda G | title = Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap? | journal = Front Neurosci | volume = 15 | issue = | article-number = 656475 | date = 2021 | pmid = 34121988 | pmc = 8187604 | doi = 10.3389/fnins.2021.656475 | doi-access = free | url = }}</ref> mesocarb (Sydnocarb),<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> and solriamfetol.<ref name="Hoy2023">{{cite journal | vauthors = Hoy SM | title = Solriamfetol: A Review in Excessive Daytime Sleepiness Associated with Narcolepsy and Obstructive Sleep Apnoea | journal = CNS Drugs | volume = 37 | issue = 11 | pages = 1009–1020 | date = November 2023 | pmid = 37847434 | doi = 10.1007/s40263-023-01040-5 | url = https://figshare.com/articles/online_resource/Solriamfetol_A_Review_in_Excessive_Daytime_Sleepiness_Associated_with_Narcolepsy_and_Obstructive_Sleep_Apnoea/24086931}}</ref>

====Other actions==== Phenylpiracetam binds to α4β2 nicotinic acetylcholine receptors in the mouse brain cortex with an {{Abbrlink|IC50|half-maximal inhibitory concentration}} of 5.86{{nbsp}}μM.<ref name="GromovaTorshin2024" /><ref name="FirstovaAbaimovAbaimov2011" /><ref name="ZhaoKuryatovLindstrom2001">{{cite journal | vauthors = Zhao X, Kuryatov A, Lindstrom JM, Yeh JZ, Narahashi T | title = Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons | journal = Mol Pharmacol | volume = 59 | issue = 4 | pages = 674–683 | date = April 2001 | pmid = 11259610 | doi = 10.1124/mol.59.4.674 | url = }}</ref>

Racetams generally, but including phenylpiracetam, have been described as AMPA receptor potentiators.<ref name="KadriuMusazziJohnston2021">{{cite journal | vauthors = Kadriu B, Musazzi L, Johnston JN, Kalynchuk LE, Caruncho HJ, Popoli M, Zarate CA | title = Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road | journal = Drug Discov Today | volume = 26 | issue = 12 | pages = 2816–2838 | date = December 2021 | pmid = 34358693 | pmc = 9585480 | doi = 10.1016/j.drudis.2021.07.027 | url = }}</ref>

====Animal studies==== Research on animals has indicated that phenylpiracetam may have antiamnesic, antidepressant, anxiolytic, and anticonvulsant effects.<ref name="MalykhSadaie2010" /><ref name="ZvejnieceSvalbeVeinberg2011">{{cite journal | vauthors = Zvejniece L, Svalbe B, Veinberg G, Grinberga S, Vorona M, Kalvinsh I, Dambrova M | title = Investigation into stereoselective pharmacological activity of phenotropil | journal = Basic & Clinical Pharmacology & Toxicology | volume = 109 | issue = 5 | pages = 407–412 | date = November 2011 | pmid = 21689376 | doi = 10.1111/j.1742-7843.2011.00742.x | doi-access = free }}</ref> Additional clinical research is necessary to determine whether these effects extend to humans.

Phenylpiracetam has been shown to reverse the sedative or depressant effects of the benzodiazepine diazepam, increases operant behavior, inhibits post-rotational nystagmus, prevents retrograde amnesia, and has anticonvulsant properties in animal models.<ref name="MalykhSadaie2010" /><ref name="Voronina2023" /><ref name="FirstovaAbaimovAbaimov2011">{{cite journal |vauthors=Firstova YY, Abaimov DA, Kapitsa IG, Voronina TA, Kovalev GI |year=2011 |title=The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task |journal=Neurochemical Journal |volume=28 |issue=2 |pages=130–141 |doi=10.1134/S1819712411020048 |s2cid=5845024}}</ref><ref name="BobkovMorozovGlozman1983" /><ref name="AntonovaProkopovAkhapkina2003">{{cite journal | vauthors = Antonova MI, Prokopov AA, Akhapkina VI, Berlyand AS | title=Experimental Pharmacokinetics of Phenotropyl in Rats | journal=Pharmaceutical Chemistry Journal | publisher=Springer Science and Business Media LLC | volume=37 | issue=11 | year=2003 | issn=0091-150X | doi=10.1023/b:phac.0000016064.51030.6f | pages=571–572}}</ref>

In Wistar rats with gravitational cerebral ischemia, phenylpiracetam reduced the extent of neuralgic deficiency manifestations, retained the locomotor, research, and memory functions, increased the survival rate, and lead to the favoring of local cerebral flow restoration upon the occlusion of carotid arteries to a greater extent than did piracetam.<ref name="TiurenkovBagmetovEpishina2007">{{cite journal | vauthors = Tiurenkov IN, Bagmetov MN, Epishina VV | title = [Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia] | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 70 | issue = 2 | pages = 24–29 | year = 2007 | pmid = 17523446 }}</ref>

In tests against a control, Sprague-Dawley rats given free access to less-preferred rat chow and trained to operate a lever repeatedly to obtain preferred rat chow performed additional work when given methylphenidate, dextroamphetamine, and phenylpiracetam.<ref name="EP20140000021" /> Rats administered 100{{nbsp}}mg/kg phenylpiracetam performed, on average, 375% more work than rats given placebo, and consumed little non-preferred rat chow.<ref name="EP20140000021" /> In comparison, rats administered 1mg/kg dextroamphetamine or 10{{nbsp}}mg/kg methylphenidate performed, on average, 150% and 170% more work respectively, and consumed half as much non-preferred rat chow.<ref name="EP20140000021" />

{{quote|Present data show that (''R'')-phenylpiracetam increases motivation, i.e., the work load, which animals are willing to perform to obtain more rewarding food. At the same time consumption of freely available normal food does not increase. Generally this indicates that (''R'')-phenylpiracetam increase motivation [...] The effect of (''R'')-phenylpiracetam is much stronger than that of methylphenidate and amphetamine.<ref name="EP20140000021">{{cite patent | country=EP | number=20140000021 | status=application | title=Use of (r)-phenylpiracetam for the treatment of sleep disorders | pubdate=2015-07-08 | fdate=2014-01-03 | pridate=2014-01-03 | url=https://www.google.com/patents/EP2891491A1 | assign1 = Merz Pharma GmbH and Co KGaA }}</ref>}}

===Pharmacokinetics=== The pharmacokinetics of phenylpiracetam in humans are unpublished.<ref name="GromovaTorshin2024" /> In any case, the drug is described as having an oral bioavailability of approximately 100%, as having an onset of action of less than 1{{nbsp}}hour, as not being metabolized, as being excreted unchanged about 40% in urine and 60% in bile and sweat, and as having an elimination half-life of 3 to 5{{nbsp}}hours.<ref name="MalykhSadaie2010" /><ref name="Phenylpiracetam-Leaflet" /> In rodents, its absorption occurs within 1{{nbsp}}hour with oral administration or intramuscular injection and its elimination half-life is 2.5 to 3{{nbsp}}hours.<ref name="MalykhSadaie2010" />

==Chemistry== Phenylpiracetam, also known as 4-phenylpiracetam, is a racetam (i.e., a 2-oxo-1-pyrrolidine acetamide derivative) and the 4-phenyl-substituted analogue of piracetam.<ref name="MalykhSadaie2010" /><ref name="BobkovMorozovGlozman1983">{{cite journal | vauthors = ((Bobkov Iu)), Morozov IS, Glozman OM, Nerobkova LN, Zhmurenko LA | title = [Pharmacological characteristics of a new phenyl analog of piracetam--4-phenylpiracetam] | language = Russian | journal = Biull Eksp Biol Med | volume = 95 | issue = 4 | pages = 50–53 | date = April 1983 | pmid = 6403074 | doi = 10.1007/BF00838859| url = }}</ref> In contrast to piracetam and most other racetams however, phenylpiracetam contains β-phenylethylamine within its chemical structure and hence can additionally be conceptualized as a substituted phenethylamine.<ref name="PubChem">{{cite web | title=Fonturacetam | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/132441 | access-date=27 September 2024}}</ref>

Phenylpiracetam is a racemic mixture of (''R'')- and (''S'')-enantiomers, (''R'')-phenylpiracetam (MRZ-9547) and (''S'')-phenylpiracetam.<ref name="PubChem" /><ref name="VeinbergVaversOrlova2015" /><ref name="SommerDanyszRuss2014" /><ref name="ZvejnieceSvalbeVavers2017" />

===Derivatives=== RGPU-95 (4-chlorophenylpiracetam) is a derivative of phenylpiracetam described as having 5- to 10-fold greater potency.<ref name="Aipsin">{{cite web | title=102. п-Хлорфенилпирацетам (RGPU-95, p-Cl-Phenylpiracetam) | trans-title=102. p-Chlorophenylpiracetam (RGPU-95, p-Cl-Phenylpiracetam) | website=АИПСИН | url=https://aipsin.com/newsubstance/434/ | language=ru | access-date=26 September 2024 | quote=p-Chlorophenylpiracetam is a synthetic substance that is a derivative of phenylpiracetam, a nootropic drug widely used for recreational purposes. The compound, along with other analogues, was developed to obtain more powerful analogues of phenylpiracetam for the treatment of anxiety disorders. The effect of p-chlorophenylpiracetam on the human body has not been thoroughly studied. Experiments on laboratory animals have shown that the substance has the properties of an anxiolytic, antidepressant, nootropic, and in its activity, p-chlorophenylpiracetam is 5-10 times more active than phenipiracetam, therefore, the recommended doses of the substance are about 10-60 mg. Based on the few data on specialized forums, the substance begins to act 10-15 minutes after oral administration, maximum effects are achieved after 1-3 hours, the duration of action is more than 6 hours. The prevalence of the compound is currently not great due to the presence of more studied analogs on the market. Nevertheless, p-chlorophenylpiracetam has a high social danger due to its properties and the effects it has on the body. Monitoring of the spread continues.}}</ref><ref name="TiurenkovBagmetovaShishkina2010">{{cite journal | vauthors = Tiurenkov IN, Bagmetova VV, Shishkina AV, Berestovitskaia VM, Vasil'eva OS, Ostrogliadov ES | title = [Gender differences in action Fenotropil and its structural analog--compound RGPU-95 on anxiety-depressive behavior animals] | language = Russian | journal = Eksp Klin Farmakol | volume = 73 | issue = 11 | pages = 10–14 | date = November 2010 | pmid = 21254591 | doi = | url = }}</ref> Cebaracetam (CGS-25248; ZY-15119) is a derivative of RGPU-95 in which the terminal amide has been replaced with a 2-piperazinone moiety.<ref name="PubChem-Cebaracetam">{{cite web | title=Cebaracetam | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/65919 | access-date=1 October 2024}}</ref>

Methylphenylpiracetam, including all four of its stereoisomers (especially the (4''R'',5''S'')-enantiomer E1R), is a positive allosteric modulator of the sigma σ1 receptor.<ref name="VeinbergVaversOrlova2015" /><ref name="VaversZvejnieceMaurice2019">{{cite journal | vauthors = Vavers E, Zvejniece L, Maurice T, Dambrova M | title = Allosteric Modulators of Sigma-1 Receptor: A Review | journal = Front Pharmacol | volume = 10 | issue = | article-number = 223 | date = 2019 | pmid = 30941035 | pmc = 6433746 | doi = 10.3389/fphar.2019.00223 | doi-access = free | url = }}</ref><ref name="ZvejnieceVaversSvalbe2014">{{cite journal | vauthors = Zvejniece L, Vavers E, Svalbe B, Vilskersts R, Domracheva I, Vorona M, Veinberg G, Misane I, Stonans I, Kalvinsh I, Dambrova M | title = The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors | journal = Br J Pharmacol | volume = 171 | issue = 3 | pages = 761–771 | date = February 2014 | pmid = 24490863 | pmc = 3969087 | doi = 10.1111/bph.12506 | url = }}</ref> It is currently the only known racetam demonstrating σ1 receptor modulation.<ref name="VeinbergVaversOrlova2015" /> Whereas phenylpiracetam stimulates locomotor activity in animals, the E1R enantiomer of methylphenylpiracetam does not do so at doses of up to 200{{nbsp}}mg/kg.<ref name="VeinbergVaversOrlova2015" /><ref name="ZvejnieceVaversSvalbe2014" />

Phenylpiracetam hydrazide is a hydrazide derivative of phenylpiracetam described as having anticonvulsant effects.<ref name="GouliaevSenning1994" /><ref name="WangChanChang2023">{{cite journal | vauthors = Wang PL, Chan YX, Chang CC | title=New synthesis of β-aryl-GABA drugs | journal=Tetrahedron | publisher=Elsevier BV | volume=146 | year=2023 | issn=0040-4020 | doi=10.1016/j.tet.2023.133648 | article-number=133648}}</ref>

Other derivatives of phenylpiracetam have also been developed and studied.<ref name="GouliaevSenning1994" />

==History== Phenylpiracetam was first described in the scientific literature by 1983.<ref name="BobkovMorozovGlozman1983" /> It was developed in 1983 as a medication for Soviet cosmonauts to treat the prolonged stresses of working in space. Phenylpiracetam was created at the Russian Academy of Sciences Institute of Biomedical Problems in an effort led by psychopharmacologist Valentina Ivanovna Akhapkina (Валентина Ивановна Ахапкина).<ref name="MEDI-RU-Phenotropil">{{cite web |title=Фенотропил: закономерное лидерство |trans-title=Phenotropil: natural leadership |url=https://medi.ru/info/427 |url-status=dead |archive-url=https://web.archive.org/web/20170806222431/https://medi.ru/info/427 |archive-date=August 6, 2017 |access-date=July 24, 2023 |website=Medi.ru |language=ru}}</ref><ref name="AkhapkinaAkhapkin2013">{{cite journal | vauthors = Akhapkina VI, Akhapkin RV | title = [Identification and evaluation of the neuroleptic activity of phenotropil] | language = Russian | journal = Zh Nevrol Psikhiatr Im S S Korsakova | volume = 113 | issue = 7 | pages = 42–46 | date = 2013 | pmid = 23994920 | doi = | url = }}</ref> Subsequently, it became available as a prescription drug in Russia. It was approved in 2003 for treatment of various conditions.<ref name="MalykhSadaie2010" />

Pilot-cosmonaut Aleksandr Serebrov described being issued and using phenylpiracetam, as well as it being included in the Soyuz spacecraft's standard emergency medical kit, during his 197-days working in space aboard the Mir space station. He reported "the drug acts as the equalizer of the whole organism, "tidying it up", completely excluding impulsiveness and irritability inevitable in the stressful conditions of space flight."<ref name="MEDI-RU-Phenotropil" />

==Society and culture== ===Availability=== [[File:Phenotropil.jpg|thumb|alt=Phenotropil|Phenotropil 100{{nbsp}}mg from Russia.]]

While not prescribed as a pharmaceutical in the West, in Russia and certain other Eastern European countries it is available as a prescription medicine under brand names including Phenotropil (also spelled Fenotropil, Phenotropyl, and Fenotropyl), Actitropil, and Nanotropil, among others.

Phenylpiracetam is not scheduled by the United States Drug Enforcement Administration (DEA) as of 2016.<ref name="USDOJ2016">{{cite web | url = http://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf | title = List of Controlled Substances | work = Division Control Division | publisher = Drug Enforcement Administration, U.S. Department of Justice | date = 8 February 2016 | access-date = 16 September 2013 | archive-date = 17 April 2016 | archive-url = https://web.archive.org/web/20160417085659/http://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf | url-status = dead }}</ref>

===Manufacturer=== Phenylpiracetam is manufactured by the pharmaceutical companies Valenta Pharm and Pharmstandard (Pharmstandart) in Russia.<ref name="MalykhSadaie2010" /><ref name="KhatoonAlamSharma2021">{{cite journal | vauthors = Khatoon R, Alam MA, Sharma PK | title=Current approaches and prospective drug targeting to brain | journal=Journal of Drug Delivery Science and Technology | publisher=Elsevier BV | volume=61 | year=2021 | issn=1773-2247 | doi=10.1016/j.jddst.2020.102098 | article-number=102098}}</ref><ref name="Phenylpiracetam-Leaflet" />

===Doping in sport=== Phenylpiracetam has stimulant effects and may be used as a doping agent in sport.<ref name="Docherty2008">{{cite journal | vauthors = Docherty JR | title = Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA) | journal = Br J Pharmacol | volume = 154 | issue = 3 | pages = 606–622 | date = June 2008 | pmid = 18500382 | pmc = 2439527 | doi = 10.1038/bjp.2008.124 | url = }}</ref><ref name="SmithStavrosWestberg2020">{{cite journal | vauthors = Smith AC, Stavros C, Westberg K | title = Cognitive Enhancing Drugs in Sport: Current and Future Concerns | journal = Subst Use Misuse | volume = 55 | issue = 12 | pages = 2064–2075 | date = 2020 | pmid = 32525422 | doi = 10.1080/10826084.2020.1775652 | url = https://figshare.com/articles/Cognitive_enhancing_drugs_in_sport_Current_and_future_concerns/12497858}}</ref> As a result, it is on the list of stimulants banned for in-competition use by the World Anti-Doping Agency (WADA).<ref name="WADA2017" /><ref name="Docherty2008" /> This list is applicable in all Olympic sports.<ref name="WADA2017">{{cite web | title = Prohibited List | date = January 2017 | work = World Anti-Doping Agency (WADA) | url = https://www.wada-ama.org/sites/default/files/resources/files/2016-09-29_-_wada_prohibited_list_2017_eng_final.pdf | page = 6 }}</ref><ref name="EP20140000021" /> Owing to its unique stimulant properties among racetams, phenylpiracetam is the only racetam on the WADA prohibited list.<ref name="SmithStavrosWestberg2020" />

==Research== Phenylpiracetam has been studied in the treatment of stroke and glaucoma.<ref name="MalykhSadaie2010" />

The more active enantiomer of phenylpiracetam, (''R'')-phenylpiracetam, was under development for fatigue related to Parkinson's disease.<ref name="AdisInsight-MRZ-9547">{{cite web | title=MRZ 9547 | website=AdisInsight | date=4 November 2017 | url=https://adisinsight.springer.com/drugs/800044857 | access-date=11 August 2024}}</ref> However, no recent development has been reported.<ref name="AdisInsight-MRZ-9547" /> There was also interest in the compound for fatigue related to depression and other conditions, but this was not pursued.<ref name="StutzGolaniWitkin2019">{{cite journal | vauthors = Stutz PV, Golani LK, Witkin JM | title = Animal models of fatigue in major depressive disorder | journal = Physiology & Behavior | volume = 199 | issue = | pages = 300–305 | date = February 2019 | pmid = 30513290 | doi = 10.1016/j.physbeh.2018.11.042 | quote = In a study performed by Sommer et al. (2014), healthy rats treated with the selective dopamine transport (DAT) inhibitor MRZ-9547 (Fig. 1) chose high effort, high reward more often than their untreated matched controls. Unlike similar studies, however, depressive symptoms were not induced before treatment; rather, baseline healthy controls were compared to healthy rats treated with MRZ-9547. [...] In one study, the selective DAT inhibitor MRZ-9547 increased the number of lever presses more than untreated controls (Sommer et al., 2014). The investigators concluded that such effort-based “decision making in rodents could provide an animal model for motivational dysfunctions related to effort expenditure such as fatigue, e.g. in Parkinson's disease or major depression.” Based upon the findings with MRZ-9547, they suggested that this drug mechanism might be a valuable therapeutic entity for fatigue in neurological and neuropsychiatric disorders. [...] A high effort bias been reported with bupropion (Randall et al., 2015), lisdexamfetamine (Yohn etal., 2016e), and the DA uptake blockers MRZ-9547 (Sommer et al., 2014), PRX-14040 (Fig. 1) (Yohn et al., 2016d) and GBR12909 (Fig. 1) (Yohn et al., 2016c). }}</ref><ref name="SommerDanyszRuss2014" /> (''R'')-Phenylpiracetam has been identified as a selective atypical dopamine reuptake inhibitor (DRIs), and similarly to other DRIs, shows pro-motivational effects in animals and reverses motivational deficits.<ref name="SalamoneCorrea2018">{{cite journal | vauthors = Salamone JD, Correa M | title=Neurobiology and pharmacology of activational and effort-related aspects of motivation: rodent studies | journal=Current Opinion in Behavioral Sciences | volume=22 | date=2018 | doi=10.1016/j.cobeha.2018.01.026 | pages=114–120 | quote = Several drugs that reverse the effects of tetrabenazine also can increase selection of high-effort PROG lever pressing when administered alone, including MSX-3 [27], and the DA transport blockers MRZ-9547 [26], bupropion [28], lisdexamfetamine [45], PRX-14040 [46], and GBR12909 [53].}}</ref><ref name="SalamoneEcevitogluCarratala-Ros2022">{{cite journal | vauthors = Salamone JD, Ecevitoglu A, Carratala-Ros C, Presby RE, Edelstein GA, Fleeher R, Rotolo RA, Meka N, Srinath S, Masthay JC, Correa M | title = Complexities and paradoxes in understanding the role of dopamine in incentive motivation and instrumental action: Exertion of effort vs. anhedonia | journal = Brain Research Bulletin | volume = 182 | issue = | pages = 57–66 | date = May 2022 | pmid = 35151797 | doi = 10.1016/j.brainresbull.2022.01.019 | quote = Administration of TBZ reduces extracellular DA and DA D1 and D2 receptor signaling at doses that induce a low effort bias (Nunes et al. 2013). The effort-related effects of TBZ are reversible with DA agonists or drugs that block DA transport (DAT) and elevate extracellular levels of DA (Nunes et al. 2013a; Randall et al. 2014; Yohn et al. 2015a,b, 2016a,b,d; Salamone et al. 2016; Rotolo et al. 2019, 2020, 2021; Carratala-Ros et al., 2021b). Furthermore, DAT inhibitors such as lisdexamfetamine, PRX14040, MRZ-9547, GBR12909, (S)-CE-123, (S, S)-CE-158, CT 005404, as well as the catecholamine uptake inhibitor bupropion, increase selection of high-effort PROG lever pressing in rats tested on effort-based choice tasks (Sommer et al. 2014; Randall et al. 2015; Yohn et al. 2016a,b,d,e; Rotolo et al. 2019, 2020, 2021). | hdl = 10234/200412 | hdl-access = free }}</ref><ref name="SommerDanyszRuss2014" />

==See also== * Phensuximide – a succinimide analogue * Phenibut – also included in Russian cosmonaut medical kits * List of Russian drugs

==References== {{Reflist}}

==Further reading== * {{cite journal | vauthors = Arsenyeva KE | title = Опыт применения Фенотропила в клинической практике | trans-title = The Experience of Using Phenotropil in Clinical Practice | journal = РМЖ (Русский Медицинский Журнал) | trans-journal = RMS (Russian Medical Journal) | date = 18 March 2007 | volume = | issue = 6 | page = 519 | language = ru | issn = 2225-2282 | format = HTML | url = https://www.rmj.ru/articles/nevrologiya/Opyt_primeneniya_Fenotropila_v_klinicheskoy_praktike/}}

==External links== * [https://www.rmj.ru/search/?q=%D0%A4%D0%B5%D0%BD%D0%BE%D1%82%D1%80%D0%BE%D0%BF%D0%B8%D0%BB%D0%B0&THEME=ALL&ARTICLE_SEARCH=Y "Фенотропила" (Phenotropil) Search in the Russian Medical Journal]

{{Racetams}} {{Stimulants}} {{Anti-dementia drugs}} {{Anticonvulsants}} {{Monoamine reuptake inhibitors}} {{Nicotinic acetylcholine receptor modulators}} {{Phenethylamines}} {{Chemical classes of psychoactive drugs}}

Category:Acetamides Category:Anticonvulsants Category:Antidepressants Category:Anxiolytics Category:Drugs in sport Category:Drugs in the Soviet Union Category:Drugs with unknown mechanisms of action Category:Nicotinic agonists Category:Nootropics Category:Norepinephrine–dopamine reuptake inhibitors Category:Phenethylamines Category:Pro-motivational agents Category:Racetams Category:Russian drugs Category:Russian inventions Category:Stimulants Category:Wakefulness-promoting agents Category:World Anti-Doping Agency prohibited substances