Dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter.[1] Dopaminergic substances or actions increase dopamine-related activity in the brain.
Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well.
Also, any endogenous or exogenous chemical substance that 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 have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.
Dopaminergic agents
[edit]Dopamine precursors
[edit]Dopamine precursors including L-phenylalanine and L-tyrosine are used as dietary supplements. L-DOPA (Levodopa), another precursor, is used in the treatment of Parkinson's disease.
Dopamine receptor agonists
[edit]Dopamine receptor agonists such as apomorphine, bromocriptine, cabergoline, dihydrexidine (LS-186,899), dopamine, fenoldopam, piribedil, lisuride, pergolide, pramipexole, ropinirole, and rotigotine, are used in the treatment of Parkinson's disease and to treat depression and anxiety.
Dopamine receptor agonists can be divided into D1-like receptor agonists and D2-like receptor agonists.
Dopamine receptor positive allosteric modulators
[edit]Positive allosteric modulators of the dopamine D1 receptor like mevidalen and glovadalen are under development for the treatment of Lewy body disease and Parkinson's disease.
Dopamine receptor antagonists
[edit]Dopamine receptor antagonists including typical antipsychotics such as chlorpromazine (Thorazine), fluphenazine, haloperidol (Haldol), loxapine, molindone, perphenazine, pimozide, thioridazine, thiothixene, and trifluoperazine, the atypical antipsychotics such as amisulpride, clozapine, olanzapine, quetiapine (Seroquel), risperidone (Risperdal), sulpiride, and ziprasidone, and antiemetics like domperidone, metoclopramide, and prochlorperazine, among others, which are used in the treatment of schizophrenia and bipolar disorder as antipsychotics, and nausea and vomiting.
Dopamine receptor agonists can be divided into D1-like receptor agonists and D2-like receptor antagonists. Ecopipam is an example of a D1-like receptor antagonist.
Dopamine reuptake inhibitors
[edit]Dopamine reuptake inhibitors (DRIs) or dopamine transporter (DAT) inhibitors such as methylphenidate (Ritalin), amineptine, nomifensine, cocaine, bupropion, modafinil, and vanoxerine, among others, which are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy as psychostimulants, obesity as anorectics, depression and anxiety as antidepressants and anxiolytics, respectively, fatigue, drug addiction as anticraving agents, and sexual dysfunction, as well as illicit street drugs.
Dopamine depleting agents
[edit]Vesicular monoamine transporter 2 (VMAT2) inhibitors such as reserpine, tetrabenazine, valbenazine and deutetrabenazine act as dopamine depleting agents and are used as sympatholytics or antihypertensives, to treat tardive dyskinesia, and in the past as antipsychotics. They have been associated with side effects including depression, apathy, fatigue, amotivation, and suicidality.
Dopamine releasing agents
[edit]Dopamine releasing agents (DRAs) such as phenethylamine, amphetamine, lisdexamfetamine (Vyvanse), methamphetamine, methylenedioxymethamphetamine (MDMA), phenmetrazine, pemoline, 4-methylaminorex (4-MAR), and benzylpiperazine, among many others, which, like DRIs, are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy as psychostimulants, obesity as anorectics, depression and anxiety as antidepressants and anxiolytics respectively, drug addiction as anticraving agents, and sexual dysfunction as aphrodisiacs. Many of these compounds are also illicit street drugs.
Dopaminergic activity enhancers
[edit]Dopaminergic activity enhancers such as the prescription drug selegiline (deprenyl) and the research chemicals BPAP and PPAP enhance the action potential-mediated release of dopamine.[2] This is in contrast to dopamine releasing agents like amphetamine, which induce the uncontrolled release of dopamine regardless of electrical stimulation.[2] The effects of the activity enhancers may be mediated by intracellular TAAR1 agonism coupled with uptake into monoaminergic neurons by monoamine transporters.[3][4] Dopaminergic activity enhancers are of interest in the potential treatment of a number of medical disorders, such as depression and Parkinson's disease. To date, only phenylethylamine, tryptamine, and tyramine have been identified as endogenous activity enhancers.[2]
Monoamine oxidase inhibitors
[edit]Monoamine oxidase (MAO) inhibitors (MAOIs) including non-selective agents such as phenelzine, tranylcypromine, isocarboxazid, and pargyline, MAOA selective agents like moclobemide and clorgyline, and MAOB selective agents such as selegiline and rasagiline, as well as the harmala alkaloids like harmine, harmaline, tetrahydroharmine, harmalol, harman, and norharman, which are found to varying degrees in Nicotiana tabacum (tobacco), Banisteriopsis caapi (ayahuasca, yage), Peganum harmala (Harmal, Syrian Rue), Passiflora incarnata (Passion Flower), and Tribulus terrestris, among others, which are used in the treatment of depression and anxiety as antidepressants and anxiolytics, respectively, in the treatment of Parkinson's disease and dementia, and for the recreational purpose of boosting the effects of certain drugs like phenethylamine (PEA) and psychedelics like dimethyltryptamine (DMT) via inhibiting their metabolism.
Catechol O-methyltransferase inhibitors
[edit]Catechol O-methyl transferase (COMT) inhibitors such as entacapone, opicapone, and tolcapone, which are used in the treatment of Parkinson's disease. Entacapone and opicapone are peripherally selective, but tolcapone significantly crosses the blood–brain barrier. Tolcapone is under study for potential treatment of certain psychiatric disorders such as obsessive–compulsive disorder and schizophrenia.[5][6][7]
Other enzyme inhibitors
[edit]Dopamine β-hydroxylase inhibitors like disulfiram (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 an anticraving agent, because it does not decrease craving for drugs. Instead, positive punishment from its unpleasant effects deters drug consumption.[8]
Phenylalanine hydroxylase inhibitors like 3,4-dihydroxystyrene), which is currently only a research chemical with no suitable therapeutic indications, likely because such drugs would induce the potentially highly dangerous hyperphenylalaninemia or phenylketonuria.
Tyrosine hydroxylase inhibitors like metirosine, which is used in the treatment of pheochromocytoma as a sympatholytic or antihypertensive agent.
Aromatic L-amino acid decarboxylase (AAAD) or DOPA decarboxylase inhibitors including benserazide, carbidopa, and methyldopa, which are used in the treatment of Parkinson's disease in augmentation of L-DOPA to block the peripheral conversion of dopamine, thereby inhibiting undesirable side-effects, and as sympatholytic or antihypertensive agents.
Miscellaneous agents
[edit]Tyrosine hydroxylase (TH) upregulators such as bromantane and low-dose aspirin through an unknown mechanism of action.[9][10] Bromantane's upregulation of TH may persist for a time (up to at least one month) after its discontinuation based on data related to its efficacy in treating asthenic disorders in Russia.[11]
Amantadine has dopaminergic effects through uncertain mechanisms of action.[12][13] It is structurally related to other adamantanes like bromantane and rimantadine, which also have dopaminergic actions.[14] Like bromantane, amantadine can upregulate tyrosine hydroxylase, but it is unclear whether this is involved in or responsible for its dopaminergic actions.[12]
Others such as hyperforin and adhyperforin (both found in Hypericum perforatum St. John's Wort), L-theanine (found in Camellia sinensis, the tea plant), and S-adenosyl-L-methionine (SAMe)
See also
[edit]References
[edit]- ^ Melinosky C (27 November 2022). "Parkinson's Disease: Glossary of Terms". WebMD.
- ^ a b c Shimazu 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. PMID 15093948. S2CID 37564231.
- ^ 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. PMC 9369307. PMID 35955676.
- ^ 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. PMC 10487936. PMID 37686140.
- ^ 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. PMID 38487834.
- ^ 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. PMC 7611531. PMID 34310432.
- ^ 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. PMID 17579498.
- ^ 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. PMID 16433735.
- ^ 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. PMC 6401361. PMID 30187283.
- ^ 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. PMID 17854844. S2CID 43661752.
- ^ 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. PMID 21322821.
- ^ a b Huber TJ, Dietrich DE, Emrich HM (March 1999). "Possible use of amantadine in depression". Pharmacopsychiatry. 32 (2): 47–55. doi:10.1055/s-2007-979191. PMID 10333162.
- ^ 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. PMC 7901515. PMID 33624170.
- ^ 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. PMID 38128028.