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Dopaminergic

Dopaminergicmeans "related todopamine"(literally," working on dopamine "), a commonneurotransmitter.[1]Dopaminergic substances or actions increase dopamine-related activity in the brain.

Thechemical structureof theneurotransmitterdopamine
Look updopaminergicin Wiktionary, the free dictionary.

Dopaminergic brain pathwaysfacilitate dopamine-related activity. For example, certainproteinssuch as thedopamine transporter(DAT),vesicular monoamine transporter 2(VMAT2), anddopamine receptorscan be classified as dopaminergic, andneuronsthatsynthesizeor contain dopamine andsynapseswith dopamine receptors in them may also be labeled asdopaminergic.Enzymesthat regulate thebiosynthesisormetabolismof dopamine such asaromatic L-amino acid decarboxylaseorDOPA decarboxylase,monoamine oxidase(MAO), andcatecholO-methyl transferase(COMT) may be referred to asdopaminergicas well.

Also, anyendogenousorexogenouschemical substancethat acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to havedopaminergiceffects, two prominent examples beingopioids,which enhance dopamine release indirectly in thereward pathways,and somesubstituted amphetamines,which enhance dopamine release directly by binding to and inhibitingVMAT2.

Dopaminergic agents

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See also:List of dopaminergic drugs

Dopamine precursors

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Main article:Monoamine precursor

DopamineprecursorsincludingL-phenylalanineandL-tyrosineare used asdietary supplements.L-DOPA(Levodopa), another precursor, is used in the treatment ofParkinson's disease.Prodrugsof levodopa, includingmelevodopa,etilevodopa,foslevodopa,andXP-21279also exist. They are inactive themselves but are converted into dopamine and hence act as non-selective dopamine receptor agonists.

Dopamine receptor ligands

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Dopamine receptor agonists

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Main article:Dopamine receptor agonist

Dopamine receptor agonistscan be divided intonon-selectivedopamine receptor agonists,D1-like receptoragonists, andD2-like receptoragonists.

Non-selective dopamine receptor agonists includedopamine,deoxyepinephrine(epinine),dinoxyline,anddopexamine.They are mostlyperipherally selective drugs,are often alsoadrenergic receptor agonists,and are used to treat certaincardiovascular conditions.

D2-like receptor agonists include theergolinesbromocriptine,cabergoline,dihydroergocryptine,ergoloid,lisuride,metergoline,pergolide,quinagolide,andterguride;themorphineanalogueapomorphine;and the structurally distinct agentspiribedil,pramipexole,ropinirole,rotigotine,andtalipexole.Some of these agents also have weak affinity for the D1-like receptors. They are used to treatParkinson's disease,restless legs syndrome,hyperprolactinemia,prolactinomas,acromegaly,erectile dysfunction,and forlactation suppression.They are also being studied in the treatment ofdepressionand are sometimes used in the treatment ofdisorders of diminished motivationlikeapathy,abulia,andakinetic mutism.

D1-like receptor agonists include6-Br-APB,A-68930,A-77636,A-86929,adrogolide,dihydrexidine,dinapsoline,doxanthrine,fenoldopam,razpipadon,SKF-81,297,SKF-82,958,SKF-89,145,tavapadon,andtrepipam.They have been researched for and are under development for the treatment ofParkinson's diseaseanddementia-related apathy.Peripherally selective D1-like receptor agonists like fenoldopam are used to treathypertensive crisis.

Dopamine receptor positive allosteric modulators

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Positive allosteric modulatorsof the dopamineD1receptorlikemevidalenandglovadalenare under development for the treatment ofLewy body diseaseandParkinson's disease.

Dopamine receptor antagonists

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Main article:Dopamine receptor antagonist

Dopamine receptor antagonistsincludingtypical antipsychoticssuch aschlorpromazine(Thorazine),fluphenazine,haloperidol(Haldol),loxapine,molindone,perphenazine,pimozide,thioridazine,thiothixene,andtrifluoperazine,theatypical antipsychoticssuch asamisulpride,clozapine,olanzapine,quetiapine(Seroquel),risperidone(Risperdal),sulpiride,andziprasidone,andantiemeticslikedomperidone,metoclopramide,andprochlorperazine,among others, which are used in the treatment ofschizophreniaandbipolar disorderasantipsychotics,andnauseaandvomiting.

Dopamine receptor antagonists can be divided intoD1-like receptorantagonists andD2-like receptorantagonists.Ecopipamis an example of a D1-like receptor antagonist.

At low doses, dopamineD2andD3receptorantagonists can preferentially blockpresynapticdopamine D2and D3autoreceptorsand thereby increase dopamine levels and enhance dopaminergic neurotransmission.[2][3][4]Examples of dopamine D2and D3receptor antagonists which have been used in this way includeamisulpride,[3][5][6]sulpiride,[7][8][9][10]andENX-104.[11][12]

Dopamine receptor negative allosteric modulators

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Negative allosteric modulatorsof the dopamine receptors, such asSB269652,have been identified and are being researched.[13][14][15][16]

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Dopamine reuptake inhibitors

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Main article:Dopamine reuptake inhibitor

Dopamine reuptake inhibitors(DRIs) ordopamine transporter(DAT) inhibitors such asmethylphenidate(Ritalin),amineptine,nomifensine,cocaine,bupropion,modafinil,armodafinil,phenylpiracetam,mesocarb,andvanoxerine,among others. They are used in the treatment ofattention-deficit hyperactivity disorder(ADHD) aspsychostimulants,narcolepsyaswakefulness-promoting agents,obesityandbinge eating disorderasappetite suppressants,depressionasantidepressants,andfatigueaspro-motivational agents.They are also used asillicitstreetandrecreational drugsdue to theireuphoriantand psychostimulant effects.

Dopamine releasing agents

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Main article:Dopamine releasing agent

Dopamine releasing agents(DRAs) such asphenethylamine,amphetamine,lisdexamfetamine(Vyvanse),methamphetamine,methylenedioxymethamphetamine(MDMA),phenmetrazine,pemoline,4-methylaminorex(4-MAR),phentermine,andbenzylpiperazine,among many others, which, like DRIs, are used in the treatment ofattention-deficit hyperactivity disorder(ADHD) andnarcolepsyaspsychostimulants,obesityasanorectics,depressionandanxietyasantidepressantsandanxiolyticsrespectively,drug addictionasanticraving agents,andsexual dysfunctionasaphrodisiacs.Many of these compounds are alsoillicitstreetorrecreational drugs.

Dopaminergic activity enhancers

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Main article:Monoaminergic activity enhancer

Dopaminergic activity enhancerssuch as theprescription drugselegiline(deprenyl) and theresearch chemicalsBPAPandPPAPenhance theaction potential-mediated release of dopamine.[17]This is in contrast to dopamine releasing agents like amphetamine, which induce the uncontrolled release of dopamine regardless of electrical stimulation.[17]The effects of the activity enhancers may be mediated byintracellularTAAR1agonismcoupled with uptake into monoaminergic neurons bymonoamine transporters.[18][19]Dopaminergic activity enhancers are of interest in the potential treatment of a number ofmedical disorders,such asdepressionandParkinson's disease.To date, onlyphenylethylamine,tryptamine,andtyraminehave been identified as endogenous activity enhancers.[17]

Dopamine depleting agents

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Main article:Monoamine depleting agent

Vesicular monoamine transporter 2(VMAT2) inhibitors such asreserpine,tetrabenazine,valbenazine,anddeutetrabenazineact asdopamine depleting agentsand are used assympatholyticsorantihypertensives,to treattardive dyskinesia,and in the past asantipsychotics.They have been associated with side effects includingdepression,apathy,fatigue,amotivation,andsuicidality.

Dopamine metabolism modulators

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Monoamine oxidase inhibitors

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Main article:Monoamine oxidase inhibitor

Monoamine oxidase(MAO)inhibitors(MAOIs) includingnon-selectiveagents such asphenelzine,tranylcypromine,isocarboxazid,andpargyline,MAOAselectiveagents likemoclobemideandclorgyline,andMAOBselectiveagents such asselegilineandrasagiline,as well as theharmala alkaloidslikeharmine,harmaline,tetrahydroharmine,harmalol,harman,andnorharman,which are found to varying degrees inNicotiana tabacum(tobacco),Banisteriopsis caapi(ayahuasca, yage),Peganum harmala(Harmal, Syrian Rue),Passiflora incarnata(Passion Flower), andTribulus terrestris,among others, which are used in the treatment ofdepressionandanxietyasantidepressantsandanxiolytics,respectively, in the treatment ofParkinson's diseaseanddementia,and for therecreationalpurpose of boosting the effects of certaindrugslikephenethylamine(PEA) andpsychedelicslikedimethyltryptamine(DMT) via inhibiting theirmetabolism.

CatecholO-methyltransferase inhibitors

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Main article:Catechol-O-methyltransferase inhibitor

CatecholO-methyl transferase(COMT)inhibitorssuch asentacapone,opicapone,andtolcapone,which are used in the treatment ofParkinson's disease.Entacapone and opicapone areperipherally selective,but tolcapone significantly crosses theblood–brain barrier.Tolcapone is under study for potential treatment of certainpsychiatric disorderssuch asobsessive–compulsive disorderandschizophrenia.[20][21][22]

AromaticL-amino acid decarboxylase inhibitors

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Main article:Aromatic L-amino acid decarboxylase inhibitor

Aromatic L-amino acid decarboxylase(AAAD) orDOPA decarboxylase inhibitorsincludingbenserazide,carbidopa,andmethyldopa,which are used in the treatment ofParkinson's diseaseinaugmentationofL-DOPAto block theperipheralconversion ofdopamine,thereby inhibiting undesirableside-effects,and assympatholyticorantihypertensiveagents.

Dopamine β-hydroxylase inhibitors

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Dopamine β-hydroxylaseinhibitors likedisulfiram(Antabuse), which can be used in the treatment of addiction to cocaine and similar dopaminergic drugs as a deterrent drug. The excess dopamine resulting from inhibition of the dopamine β-hydroxylase enzyme increases unpleasant symptoms such as anxiety, higher blood pressure, and restlessness. Disulfiram is not ananticraving agent,because it does not decrease craving for drugs. Instead,positive punishmentfrom its unpleasant effects deters drug consumption.[23]Other dopamine β-hydroxylase inhibitors include the centrally activenepicastatand theperipherally selectiveetamicastatandzamicastat.

Other enzyme inhibitors

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Phenylalanine hydroxylaseinhibitors like3,4-dihydroxystyrene), which is currently only aresearch chemicalwith no suitable therapeutic indications, likely because such drugs would induce the potentially highly dangeroushyperphenylalaninemiaorphenylketonuria.

Tyrosine hydroxylaseinhibitors likemetirosine,which is used in the treatment ofpheochromocytomaas asympatholyticorantihypertensiveagent.

Dopaminergic neurotoxins

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Dopaminergic neurotoxinslike6-hydroxydopamine(6-OHDA) andMPTPare used inscientific researchtolesionthe dopamine system and study the biological role of dopamine.

Miscellaneous agents

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Adamantane derivatives

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Amantadinehas dopaminergic effects through uncertainmechanisms of action.[24][25]It is structurally related to otheradamantaneslikebromantaneandrimantadine,which also have dopaminergic actions.[26]Bromantane can upregulatetyrosine hydroxylase(TH) and thereby increase dopamine production and this might be involved in its dopaminergic effects.[27][28]Amantadine can upregulate TH similarly, but as with bromantane, it is unclear whether this is involved in or responsible for its dopaminergic actions.[24]Amantadine is used in the treatment ofParkinson's disease,levodopa-induced dyskinesia,andfatigueinmultiple sclerosis.It has also been used in the treatment ofdisorders of consciousness,disorders of diminished motivation,andbrain injuries.The drug is being studied in the treatment ofdepressionandattention deficit hyperactivity disorder(ADHD) as well.

Diphenylpiperidines

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4,4-Diphenylpiperidines includingbudipineandprodipineare effective in the treatment ofParkinson's disease.[29][30][31]Theirmechanism of actionis unknown but they act as indirect dopaminergic agents.[30][29][31]They have distinct effects from other antiparkinsonian agents and dopaminergic drugs.[30][29][31]

Other miscellaneous agents

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Aspirinupregulatestyrosine hydroxylaseand increases dopamine production.[32]

Others such ashyperforinandadhyperforin(both found inHypericum perforatumSt. John's Wort),L-theanine(found inCamellia sinensis,the tea plant), andS-adenosyl-L-methionine(SAMe).

See also

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References

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  1. ^Melinosky C (27 November 2022)."Parkinson's Disease: Glossary of Terms".WebMD.
  2. ^Möller HJ (June 2005). "Antipsychotic and antidepressive effects of second generation antipsychotics: two different pharmacological mechanisms?".Eur Arch Psychiatry Clin Neurosci.255(3): 190–201.doi:10.1007/s00406-005-0587-5.PMID15995903.
  3. ^abCurran MP, Perry CM (2002). "Spotlight on amisulpride in schizophrenia".CNS Drugs.16(3): 207–211.doi:10.2165/00023210-200216030-00007.PMID11888341.
  4. ^Pani L, Gessa GL (2002). "The substituted benzamides and their clinical potential on dysthymia and on the negative symptoms of schizophrenia".Mol Psychiatry.7(3): 247–253.doi:10.1038/sj.mp.4001040.PMID11920152.
  5. ^McKeage K, Plosker GL (2004). "Amisulpride: a review of its use in the management of schizophrenia".CNS Drugs.18(13): 933–956.doi:10.2165/00023210-200418130-00007.PMID15521794.
  6. ^Wu J, Kwan AT, Rhee TG, Ho R, d'Andrea G, Martinotti G, Teopiz KM, Ceban F, McIntyre RS (2023). "A narrative review of non-racemic amisulpride (SEP-4199) for treatment of depressive symptoms in bipolar disorder and LB-102 for treatment of schizophrenia".Expert Rev Clin Pharmacol.16(11): 1085–1092.doi:10.1080/17512433.2023.2274538.PMID37864424.
  7. ^Serra G, Forgione A, D'Aquila PS, Collu M, Fratta W, Gessa GL (1990). "Possible mechanism of antidepressant effect of L-sulpiride".Clin Neuropharmacol.13 Suppl 1: S76–S83.doi:10.1097/00002826-199001001-00009.PMID2199037.
  8. ^Wagstaff, Antona J.; Fitton, Andrew; Benfield, Paul (1994). "Sulpiride".CNS Drugs.2(4). Springer Science and Business Media LLC: 313–333.doi:10.2165/00023210-199402040-00007.ISSN1172-7047.
  9. ^Mauri MC, Bravin S, Bitetto A, Rudelli R, Invernizzi G (May 1996). "A risk-benefit assessment of sulpiride in the treatment of schizophrenia".Drug Saf.14(5): 288–298.doi:10.2165/00002018-199614050-00003.PMID8800626.
  10. ^Ohmann HA, Kuper N, Wacker J (2020)."A low dosage of the dopamine D2-receptor antagonist sulpiride affects effort allocation for reward regardless of trait extraversion".Personal Neurosci.3:e7.doi:10.1017/pen.2020.7.PMC7327436.PMID32656492.
  11. ^Vadodaria K, Kangas BD, Garvey DS, Brubaker W, Pizzagalli DA, Sudarsan V, Vanover KE, Serrats J (December 2022)."ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P351. Anti-Anhedonic Profile of ENX-104, a Novel and Highly Potent Dopamine D2/3 Receptor Antagonist".Neuropsychopharmacology.47(Suppl 1): 220–370 (265–266).doi:10.1038/s41386-022-01485-0.PMC9714399.PMID36456694.
  12. ^Vadodaria K, Serrats J, Brubaker W, Sudarsan V, Vanover K (December 2023)."ACNP 62nd Annual Meeting: Poster Abstracts P251 - P500: P356. ENX-104, a Novel and Potent D2/3 Receptor Antagonist, Increased Extracellular Levels of Dopamine and Serotonin in the Nucleus Accumbens and Prefrontal Cortex of Freely-Moving Rats".Neuropsychopharmacology.48(Suppl 1): 211–354 (271–272).doi:10.1038/s41386-023-01756-4.PMC10729596.PMID38040810.
  13. ^Rossi M, Fasciani I, Marampon F, Maggio R, Scarselli M (June 2017)."The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs".Mol Pharmacol.91(6): 586–594.doi:10.1124/mol.116.107607.PMC5438131.PMID28265019.
  14. ^Girmaw F (March 2024)."Review on allosteric modulators of dopamine receptors so far".Health Sci Rep.7(3): e1984.doi:10.1002/hsr2.1984.PMC10948587.PMID38505681.
  15. ^Soriano A, Vendrell M, Gonzalez S, Mallol J, Albericio F, Royo M, Lluís C, Canela EI, Franco R, Cortés A, Casadó V (March 2010). "A hybrid indoloquinolizidine peptide as allosteric modulator of dopamine D1 receptors".J Pharmacol Exp Ther.332(3): 876–885.doi:10.1124/jpet.109.158824.PMID20026675.
  16. ^Shonberg J, Draper-Joyce C, Mistry SN, Christopoulos A, Scammells PJ, Lane JR, Capuano B (July 2015). "Structure-activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor".J Med Chem.58(13): 5287–5307.doi:10.1021/acs.jmedchem.5b00581.PMID26052807.
  17. ^abcShimazu S, Miklya I (May 2004). "Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives".Progress in Neuro-Psychopharmacology & Biological Psychiatry.28(3): 421–427.doi:10.1016/j.pnpbp.2003.11.016.PMID15093948.S2CID37564231.
  18. ^Harsing LG, Knoll J, Miklya I (August 2022)."Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum".Int J Mol Sci.23(15): 8543.doi:10.3390/ijms23158543.PMC9369307.PMID35955676.
  19. ^Harsing LG, Timar J, Miklya I (August 2023)."Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline".Int J Mol Sci.24(17): 13334.doi:10.3390/ijms241713334.PMC10487936.PMID37686140.
  20. ^Kings E, Ioannidis K, Grant JE, Chamberlain SR (June 2024). "A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans".CNS Spectr.29(3): 166–175.doi:10.1017/S1092852924000130.PMID38487834.
  21. ^Grant JE, Hook R, Valle S, Chesivoir E, Chamberlain SR (September 2021)."Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial".Int Clin Psychopharmacol.36(5): 225–229.doi:10.1097/YIC.0000000000000368.PMC7611531.PMID34310432.
  22. ^Apud JA, Weinberger DR (2007). "Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors".CNS Drugs.21(7): 535–557.doi:10.2165/00023210-200721070-00002.PMID17579498.
  23. ^Krampe H, Stawicki S, Wagner T, Bartels C, Aust C, Rüther E, Poser W, Ehrenreich H (January 2006). "Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome".Alcoholism: Clinical and Experimental Research.30(1): 86–95.doi:10.1111/j.1530-0277.2006.00013.x.PMID16433735.
  24. ^abHuber TJ, Dietrich DE, Emrich HM (March 1999). "Possible use of amantadine in depression".Pharmacopsychiatry.32(2): 47–55.doi:10.1055/s-2007-979191.PMID10333162.
  25. ^Danysz W, Dekundy A, Scheschonka A, Riederer P (February 2021)."Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials".J Neural Transm (Vienna).128(2): 127–169.doi:10.1007/s00702-021-02306-2.PMC7901515.PMID33624170.
  26. ^Ragshaniya A, Kumar V, Tittal RK, Lal K (March 2024). "Nascent pharmacological advancement in adamantane derivatives".Arch Pharm (Weinheim).357(3): e2300595.doi:10.1002/ardp.202300595.PMID38128028.
  27. ^Mikhaylova M, Vakhitova JV, Yamidanov RS, Salimgareeva MK, Seredenin SB, Behnisch T (October 2007). "The effects of ladasten on dopaminergic neurotransmission and hippocampal synaptic plasticity in rats".Neuropharmacology.53(5): 601–608.doi:10.1016/j.neuropharm.2007.07.001.PMID17854844.S2CID43661752.
  28. ^Voznesenskaia TG, Fokina NM, Iakhno NN (2010)."[Treatment of asthenic disorders in patients with psychoautonomic syndrome: results of a multicenter study on efficacy and safety of ladasten]".Zhurnal Nevrologii I Psikhiatrii imeni S.S. Korsakova.110(5 Pt 1): 17–26.PMID21322821.
  29. ^abcPrzuntek, H.; Stasch, J.-P. (1985). "Biochemical and Pharmacologic Aspects of the Mechanism of Action of Budipine".Clinical Experiences with Budipine in Parkinson Therapy.Berlin, Heidelberg: Springer Berlin Heidelberg. p. 107–112.doi:10.1007/978-3-642-95455-9_15.ISBN978-3-540-13764-1.
  30. ^abcPrzuntek H (April 2000). "Non-dopaminergic therapy in Parkinson's disease".J Neurol.247 Suppl 2: II19–24.doi:10.1007/pl00007756.PMID10991661.
  31. ^abcEltze M (1999). "Multiple mechanisms of action: the pharmacological profile of budipine".J Neural Transm Suppl.56:83–105.doi:10.1007/978-3-7091-6360-3_4.PMID10370904.
  32. ^Rangasamy SB, Dasarathi S, Pahan P, Jana M, Pahan K (June 2019)."Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson's Disease".Journal of Neuroimmune Pharmacology.14(2): 173–187.doi:10.1007/s11481-018-9808-3.PMC6401361.PMID30187283.
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