monoamine oxidase inhibitors

Summary

Summary: A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414)

Top Publications

  1. Gulyas B, Pavlova E, Kasa P, Gulya K, Bakota L, Varszegi S, et al. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography. Neurochem Int. 2011;58:60-8 pubmed publisher
  2. Hibbits N, Yoshino J, Le T, Armstrong R. Astrogliosis during acute and chronic cuprizone demyelination and implications for remyelination. ASN Neuro. 2012;4:393-408 pubmed publisher
    ..The astrocyte phenotype and lesion characteristics in this demyelination model inform studies to identify triggers of non-remyelinating sclerosis in chronic multiple sclerosis lesions. ..
  3. Buschmann J, Berger K, Awad H, Clarner T, Beyer C, Kipp M. Inflammatory response and chemokine expression in the white matter corpus callosum and gray matter cortex region during cuprizone-induced demyelination. J Mol Neurosci. 2012;48:66-76 pubmed publisher
    ..The same holds true for the expression of the key chemokines Ccl2 and Ccl3. The current study defines a model to study early microglia activation and to investigate differences in the neuroinflammatory response of white vs. gray matter. ..
  4. Herraiz T, Guillén H. Inhibition of the bioactivation of the neurotoxin MPTP by antioxidants, redox agents and monoamine oxidase inhibitors. Food Chem Toxicol. 2011;49:1773-81 pubmed publisher
    ..Methylene blue, 5-nitroindazole, norharman, 9-methylnorharman and menadione inhibit MAO-B in mitochondria and afford protective effects, as suggested by a reduced conversion of MPTP to neurotoxic species. ..
  5. Al Nuaimi S, MacKenzie E, Baker G. Monoamine oxidase inhibitors and neuroprotection: a review. Am J Ther. 2012;19:436-48 pubmed publisher
    b>Monoamine oxidase inhibitors have been available for more than 50 years, initially developed as antidepressants but currently used in a variety of psychiatric and neurological conditions...
  6. Binda C, Milczek E, Bonivento D, Wang J, Mattevi A, Edmondson D. Lights and shadows on monoamine oxidase inhibition in neuroprotective pharmacological therapies. Curr Top Med Chem. 2011;11:2788-96 pubmed
    ..This multi-target approach may prove successful in order to find new and more effective therapies for the complexity of neurodegenerative diseases. ..
  7. Shulman K, Herrmann N, Walker S. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs. 2013;27:789-97 pubmed publisher
    ..search of OvidSP Medline and PsycInfo performed in July 2012, using the subject terms and keywords of 'monoamine oxidase inhibitors', 'major depression', 'depressive disorder' and 'depression (emotion)'...
  8. Naoi M, Maruyama W, Inaba Hasegawa K. Type A and B monoamine oxidase in age-related neurodegenerative disorders: their distinct roles in neuronal death and survival. Curr Top Med Chem. 2012;12:2177-88 pubmed
    ..MAO-A is expected to play a role in disease-modifying therapy for neurodegenerative disorders. ..
  9. Singh M, Manton C, Bhat K, Tsai W, Aldape K, Barton M, et al. Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors. Neuro Oncol. 2011;13:894-903 pubmed publisher

More Information

Publications62

  1. Magyar K. The pharmacology of selegiline. Int Rev Neurobiol. 2011;100:65-84 pubmed publisher
    ..To circumvent the "first pass" metabolism, parenteral administration of the drug might lead to different distribution and pharmacological activity of selegiline...
  2. Goren T, Adar L, Sasson N, Weiss Y. Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline. J Clin Pharmacol. 2010;50:1420-8 pubmed publisher
    ..These data allowed removal of dietary tyramine restriction from rasagiline US labeling. ..
  3. Gillman P. Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors. J Clin Psychopharmacol. 2011;31:66-74 pubmed publisher
    Recent advances clarifying the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors that have not been considered in depth lately are discussed...
  4. Wang J, Edmondson D. Topological probes of monoamine oxidases A and B in rat liver mitochondria: inhibition by TEMPO-substituted pargyline analogues and inactivation by proteolysis. Biochemistry. 2011;50:2499-505 pubmed publisher
    ..The differential mitochondrial outer membrane topology of MAO A and MAO B is relevant to their inhibition by drugs designed to be cardioprotectants or neuroprotectants...
  5. Bolea I, Juárez Jiménez J, de Los Rios C, Chioua M, Pouplana R, Luque F, et al. Synthesis, biological evaluation, and molecular modeling of donepezil and N-[(5-(benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer. J Med Chem. 2011;54:8251-70 pubmed publisher
    ..Overall, the results suggest that the new compounds are promising multitarget drug candidates with potential impact for Alzheimer's disease therapy. ..
  6. Carradori S, Secci D, Bolasco A, Chimenti P, D Ascenzio M. Patent-related survey on new monoamine oxidase inhibitors and their therapeutic potential. Expert Opin Ther Pat. 2012;22:759-801 pubmed publisher
  7. Naoi M, Maruyama W. Monoamine oxidase inhibitors as neuroprotective agents in age-dependent neurodegenerative disorders. Curr Pharm Des. 2010;16:2799-817 pubmed
    ..This review presents the molecular mechanisms behind neuroprotection by monoamine oxidase inhibitors and discusses the possible development of new drugs to prevent, delay and restore the neuronal cell ..
  8. deMarcaida J, Schwid S, White W, Blindauer K, Fahn S, Kieburtz K, et al. Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline. Mov Disord. 2006;21:1716-21 pubmed
    ..These data demonstrate that rasagiline 0.5 to 2 mg daily is not associated with clinically significant tyramine reactions and can be used as monotherapy or adjunct to levodopa in PD patients without specific dietary tyramine restriction...
  9. Franke R, Belluzzi J, Leslie F. Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats. Psychopharmacology (Berl). 2007;195:117-24 pubmed
    ..animal model of maternal smoking, tobacco smoke contains more than 4,000 constituents, including monoamine oxidase inhibitors (MAOIs)...
  10. Hauser R, Lew M, Hurtig H, Ondo W, Wojcieszek J, Fitzer Attas C. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease. Mov Disord. 2009;24:564-73 pubmed publisher
    ..This might reflect enduring benefits due to neuroprotection or effects on compensatory mechanisms in early PD. ..
  11. Olanow C, Rascol O, Hauser R, Feigin P, Jankovic J, Lang A, et al. A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N Engl J Med. 2009;361:1268-78 pubmed publisher
    ..Because the two doses were associated with different outcomes, the study results must be interpreted with caution. (ClinicalTrials.gov number, NCT00256204.) ..
  12. Yasar S, Justinova Z, Lee S, Stefanski R, Goldberg S, Tanda G. Metabolic transformation plays a primary role in the psychostimulant-like discriminative-stimulus effects of selegiline [(R)-(-)-deprenyl]. J Pharmacol Exp Ther. 2006;317:387-94 pubmed
  13. Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson D. Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry. 2008;47:5616-25 pubmed publisher
    ..The bound arylalkyl radical reacts with the N(5) of the flavin, while the dissociated diazene reacts nonspecifically with the enzyme through arylalkylradicals. ..
  14. Stocchi F. Rasagiline: defining the role of a novel therapy in the treatment of Parkinson's disease. Int J Clin Pract. 2006;60:215-21 pubmed
  15. Vana A, Flint N, Harwood N, Le T, Fruttiger M, Armstrong R. Platelet-derived growth factor promotes repair of chronically demyelinated white matter. J Neuropathol Exp Neurol. 2007;66:975-88 pubmed
    ..Furthermore, preventing oligodendrocyte apoptosis may be important not only during active demyelination but also for supporting the generation of new oligodendrocytes to remyelinate chronic lesions. ..
  16. Eliash S, Dror V, Cohen S, Rehavi M. Neuroprotection by rasagiline in thiamine deficient rats. Brain Res. 2009;1256:138-48 pubmed publisher
    ..These findings demonstrate significant neuroprotection by rasagiline with possible implications for clinical neurodegenerative disorders. ..
  17. Lee M, Wynder C, Schmidt D, McCafferty D, Shiekhattar R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol. 2006;13:563-7 pubmed
    ..Here we show that in contrast to selective monoamine oxidase inhibitors such as pargyline, nonselective monoamine oxidase inhibitors potently inhibit nucleosomal demethylation ..
  18. Youdim M, Edmondson D, Tipton K. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci. 2006;7:295-309 pubmed
    b>Monoamine oxidase inhibitors were among the first antidepressants to be discovered and have long been used as such...
  19. Mandel S, Weinreb O, Amit T, Youdim M. Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. Brain Res Brain Res Rev. 2005;48:379-87 pubmed
    ..The neuroprotective activity of propargylamine has led us to develop novel bifunctional neuroprotective iron-chelating MAO-inhibiting drugs possessing propargyl moiety for the treatment of other neurodegenerative diseases. ..
  20. Remington L, Babcock A, Zehntner S, Owens T. Microglial recruitment, activation, and proliferation in response to primary demyelination. Am J Pathol. 2007;170:1713-24 pubmed
    ..Our study highlights the role of microglia as a heterogeneous population of cells in primary demyelination, with the capacity to present antigen, proliferate, and migrate into demyelinated areas. ..
  21. Lindner M, Heine S, Haastert K, Garde N, Fokuhl J, Linsmeier F, et al. Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination. Neuropathol Appl Neurobiol. 2008;34:105-14 pubmed
    ..Furthermore, investigation of early remyelination confirms that the intrinsic repair programme is very fast and switched on within days. ..
  22. De Colibus L, Li M, Binda C, Lustig A, Edmondson D, Mattevi A. Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B. Proc Natl Acad Sci U S A. 2005;102:12684-9 pubmed
    ..M., Soldevila, M., Navarro, A., Kidd, K. K., Oliva, B. & Bertranpetit, J. (2004) Hum. Genet. 115, 377-386]. These considerations put into question the use of MAO A from nonhuman sources in drug development for use in humans. ..
  23. Polasek T, Elliot D, Somogyi A, Gillam E, Lewis B, Miners J. An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid. Br J Clin Pharmacol. 2006;61:570-84 pubmed
    ..These data are consistent with mechanism-based inactivation of human drug-metabolizing CYP enzymes and suggest that impaired metabolic clearance may contribute to clinical drug-drug interactions with some MAO inhibitors. ..
  24. Halberstadt A, Buell M, Masten V, Risbrough V, Geyer M. Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors. Psychopharmacology (Berl). 2008;201:55-66 pubmed publisher
  25. Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T. Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. Eur J Pharmacol. 2006;532:258-64 pubmed
    ..These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline. ..
  26. Freedman N, Mishani E, Krausz Y, Weininger J, Lester H, Blaugrund E, et al. In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET. J Nucl Med. 2005;46:1618-24 pubmed
    ..Subsequent gradual recovery was also seen, with return to near-baseline uptake. This finding is compatible with the known rate of de novo synthesis of MAO-B, confirming the irreversible binding of rasagiline. ..
  27. Villegier A, Lotfipour S, McQuown S, Belluzzi J, Leslie F. Tranylcypromine enhancement of nicotine self-administration. Neuropharmacology. 2007;52:1415-25 pubmed
    ..Taken together, these results indicate that in a stringent self-administration acquisition test, MAO inhibition increases the rewarding effect of low doses of nicotine, possibly via a dopamine-dependent mechanism...
  28. Schmidt D, McCafferty D. trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry. 2007;46:4408-16 pubmed
    ..We previously assessed monoamine oxidase inhibitors (MAOIs) for their ability to inhibit the reaction catalyzed by LSD1 [Lee, M. G., et al. (2006) Chem...
  29. Liang Y, Vogel J, Narayanan A, Peng H, Kristie T. Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency. Nat Med. 2009;15:1312-7 pubmed publisher
    ..Depletion of LSD1 or inhibition of its activity with monoamine oxidase inhibitors (MAOIs) results in the accumulation of repressive chromatin and a block to viral gene expression...
  30. Alia Klein N, Goldstein R, Kriplani A, Logan J, Tomasi D, Williams B, et al. Brain monoamine oxidase A activity predicts trait aggression. J Neurosci. 2008;28:5099-104 pubmed publisher
    ..Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression...
  31. Chen J, Swope D, Dashtipour K. Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease. Clin Ther. 2007;29:1825-49 pubmed
    ..Whether rasagiline is associated with clinically significant neuroprotection (ie, disease modification) in PD is the subject of ongoing clinical trials. ..
  32. Rascol O, Brooks D, Melamed E, Oertel W, Poewe W, Stocchi F, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005;365:947-54 pubmed
    ..Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone. ..
  33. Sun G, Alzayady K, Stewart R, Ye P, Yang S, Li W, et al. Histone demethylase LSD1 regulates neural stem cell proliferation. Mol Cell Biol. 2010;30:1997-2005 pubmed publisher
    ..These findings revealed a novel role for LSD1 in neural stem cell proliferation and uncovered a mechanism for neural stem cell proliferation through recruitment of LSD1 to modulate TLX activity...
  34. Groebe A, Clarner T, Baumgartner W, Dang J, Beyer C, Kipp M. Cuprizone treatment induces distinct demyelination, astrocytosis, and microglia cell invasion or proliferation in the mouse cerebellum. Cerebellum. 2009;8:163-74 pubmed publisher
    ..Behavioral changes after cuprizone described for this animal model may not only result from effects on commissural fiber tracts but also can arise from cerebellar demyelination. ..
  35. Villegier A, Salomon L, Granon S, Changeux J, Belluzzi J, Leslie F, et al. Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine. Neuropsychopharmacology. 2006;31:1704-13 pubmed
    ..Because tobacco smoke contains monoamine oxidase inhibitors (MAOIs) and decreases MAO activity in smokers, we have combined MAOIs with nicotine to determine ..
  36. Elkashef A, Fudala P, Gorgon L, Li S, Kahn R, Chiang N, et al. Double-blind, placebo-controlled trial of selegiline transdermal system (STS) for the treatment of cocaine dependence. Drug Alcohol Depend. 2006;85:191-7 pubmed
    ..The contrast of this result to earlier, promising preclinical and human pilot data could be due to factors associated with sample size, patient characteristics, dose, or poor predictive validity of preclinical models...
  37. Guay D. Rasagiline (TVP-1012): a new selective monoamine oxidase inhibitor for Parkinson's disease. Am J Geriatr Pharmacother. 2006;4:330-46 pubmed
    ..In addition, bifunctional molecules combining selective MAO-B inhibition (based on the active moiety of rasagiline) with acetylcholinesterase inhibition or iron chelation may eventually be useful in Alzheimer's disease. ..
  38. Carpene C, Abello V, Iffiú Soltész Z, Mercier N, Feve B, Valet P. Limitation of adipose tissue enlargement in rats chronically treated with semicarbazide-sensitive amine oxidase and monoamine oxidase inhibitors. Pharmacol Res. 2008;57:426-34 pubmed publisher
    ..These observations suggest that SSAO inhibition is not sufficient to impair fat deposition. However, combined MAO and SSAO inhibition limits adiposity in non-obese as well as in obese rats. ..
  39. Thébault J, Guillaume M, Levy R. Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor. Pharmacotherapy. 2004;24:1295-305 pubmed
    ..Rasagiline is well tolerated at doses up to 20 mg once/day and is a potent inhibitor of platelet MAO-B in humans. ..
  40. Shimazu S, Minami A, Kusumoto H, Yoneda F. Antidepressant-like effects of selegiline in the forced swim test. Eur Neuropsychopharmacol. 2005;15:563-71 pubmed
    ..These results suggest that selegiline exerts the antidepressant-like effects by prolonging escape-directed behavior rather than by a motor stimulant effect and D1 receptor activation contributes to its effect...
  41. Lindner M, Fokuhl J, Linsmeier F, Trebst C, Stangel M. Chronic toxic demyelination in the central nervous system leads to axonal damage despite remyelination. Neurosci Lett. 2009;453:120-5 pubmed publisher
    ..These data suggest that two pattern of axonal injury occur in the cuprizone model. ..
  42. Lewis A, Miller J, Lea R. Monoamine oxidase and tobacco dependence. Neurotoxicology. 2007;28:182-95 pubmed
  43. Dreiseitel A, Korte G, Schreier P, Oehme A, Locher S, Domani M, et al. Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B. Pharmacol Res. 2009;59:306-11 pubmed publisher
    ..For extrapolation of the present findings to in vivo effects, future studies will need to address in more detail the bioavailability of these dietary constituents. ..
  44. Sant Anna G, Machado P, Sauzem P, Rosa F, Rubin M, Ferreira J, et al. Ultrasound promoted synthesis of 2-imidazolines in water: a greener approach toward monoamine oxidase inhibitors. Bioorg Med Chem Lett. 2009;19:546-9 pubmed publisher
  45. Schulte J, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, et al. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 2009;69:2065-71 pubmed publisher
    ..Moreover, LSD1 inhibition using monoamine oxidase inhibitors resulted in an increase of global H3K4 methylation and growth inhibition of neuroblastoma cells in ..
  46. Vilches Herrera M, Miranda Sepúlveda J, Rebolledo Fuentes M, Fierro A, Lühr S, Iturriaga Vasquez P, et al. Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors. Bioorg Med Chem. 2009;17:2452-60 pubmed publisher
    A series of naphthylisopropylamine and N-benzyl-4-methylthioamphetamine derivatives were evaluated as monoamine oxidase inhibitors. Their potencies were compared with those of a series of amphetamine derivatives, to test if the increase ..
  47. Tatsuta T, Kitanaka N, Kitanaka J, Morita Y, Takemura M. Effects of monoamine oxidase inhibitors on methamphetamine-induced stereotypy in mice and rats. Neurochem Res. 2005;30:1377-85 pubmed
    ..These results suggest that a low dose of clorgyline tends to increase the latency and decrease the intensity of stereotypies induced by METH in a dopamine metabolism-independent manner in mice. ..
  48. Ravikumar K, Sridhar B. Two polymorphs of safinamide, a selective and reversible inhibitor of monoamine oxidase B. Acta Crystallogr C. 2010;66:o317-20 pubmed publisher
    ..N-H...O hydrogen bonds are present in both structures, whereas N-H...F hydrogen bonding is seen in polymorph (I), while N-H...N hydrogen bonding is seen in polymorph (II). ..
  49. Juang H, Chen P, Chien K. Using antidepressants and the risk of stroke recurrence: report from a national representative cohort study. BMC Neurol. 2015;15:86 pubmed publisher
    ..system: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and other antidepressants. The main outcome was a recurrent stroke during the follow-up period...
  50. Wiltshire P, Hawksworth D, Edwards K. Light microscopy can reveal the consumption of a mixture of psychotropic plant and fungal material in suspicious death. J Forensic Leg Med. 2015;34:73-80 pubmed publisher
    ..The example presented here also demonstrates the need for caution in interpreting toxicological results where screening for unusual compounds has been limited. ..
  51. Branco J, Tomé A, Cruz M, Filipe A. Pirlindole in the treatment of depression and fibromyalgia syndrome. Clin Drug Investig. 2011;31:675-89 pubmed publisher
    ..The available evidence supports pirlindole as a safe and effective treatment option for the management of depression and fibromyalgia syndrome. ..
  52. Shelke S, Bhosale S, Dash R, Suryawanshi M, Mahadik K. Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening. Bioorg Med Chem Lett. 2011;21:2419-24 pubmed publisher
    ..Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition. ..
  53. Menkes D, Bosanac P, Castle D. MAOIs - does the evidence warrant their resurrection?. Australas Psychiatry. 2016;24:371-3 pubmed publisher
    The place of monoamine oxidase inhibitors (MAOIs) in psychiatry is reviewed, and the question posed as to whether they are now justifiably disregarded by prescribers...