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Journal of Parkinson's Disease 2022Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson's disease (PD). MAO-B inhibitor monotherapy has been shown to be... (Review)
Review
Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson's disease (PD). MAO-B inhibitor monotherapy has been shown to be effective and safe for the treatment of early-stage PD, while MAO-B inhibitors as adjuvant drugs have been widely applied for the treatment of the advanced stages of the illness. MAO-B inhibitors can effectively improve patients' motor and non-motor symptoms, reduce "OFF" time, and may potentially prevent/delay disease progression. In this review, we discuss the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor therapy.
Topics: Dopamine Agents; Humans; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34957948
DOI: 10.3233/JPD-212976 -
American Family Physician Dec 2020Parkinson disease is a progressive neurodegenerative disorder with significant morbidity and mortality. Most patients consult with their primary care physician about...
Parkinson disease is a progressive neurodegenerative disorder with significant morbidity and mortality. Most patients consult with their primary care physician about Parkinson disease symptoms before seeking care from a specialist. The diagnosis of Parkinson disease is clinical, and key disease features are bradykinesia, rigidity, and tremor. The main diagnostic signs of Parkinson disease are motor symptoms; however, Parkinson disease is also associated with nonmotor symptoms, including autonomic dysfunction, depression, and hallucinations, which can make the initial diagnosis of Parkinson disease difficult. Disease progression is variable and clinical signs cannot be used to predict progression accurately. Therapies, including levodopa, have not demonstrated the ability to slow disease progression. Motor symptoms are managed with carbidopa/levodopa, monoamine oxidase-B inhibitors, and nonergot dopamine agonists. Prolonged use and higher doses of levodopa result in dyskinesias and motor symptom fluctuations over time. Deep brain stimulation surgery is performed for patients who do not achieve adequate control with levodopa therapy. Deep brain stimulation is most effective for significant motor fluctuations, dyskinesias, and tremors. Nonmotor symptom therapies target patient-specific conditions during the disease course. Interdisciplinary team care can alleviate multiple symptoms of Parkinson disease.
Topics: Antiparkinson Agents; Carbidopa; Combined Modality Therapy; Deep Brain Stimulation; Disease Progression; Drug Combinations; Family Practice; Humans; Levodopa; Parkinson Disease; Physical Therapy Modalities
PubMed: 33252908
DOI: No ID Found -
Journal of Neural Transmission (Vienna,... Jun 2023Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong... (Review)
Review
Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong its effect in striatal dopaminergic neurotransmission in Parkinson's disease patients. While selegiline/rasagiline and tolcapone/entacapone have been available on the market for more than one decade, safinamide and opicapone have been approved in 2015 and 2016, respectively. Meanwhile, comprehensive data from several post-authorization studies have described the use and specific characteristics of the individual substances in clinical practice under real-life conditions. Here, we summarize current knowledge on both medication classes, with a focus on the added clinical value in Parkinson's disease. Furthermore, we outline practical considerations in the treatment of motor fluctuations and provide an outlook on ongoing studies with MAO-B and COMT inhibitors.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Monoamine Oxidase; Catechol O-Methyltransferase; Levodopa; Catechol O-Methyltransferase Inhibitors; Monoamine Oxidase Inhibitors
PubMed: 36964457
DOI: 10.1007/s00702-023-02623-8 -
Frontiers in Cardiovascular Medicine 2021Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association... (Review)
Review
Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association between depression and hypotension. This phenomenon may depend, at least in part, on the use of antidepressant drugs, which may influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems. This review summarizes extant literature on the effect of antidepressant drugs on blood pressure. Selective serotonin reuptake inhibitors are characterized by limited effects on autonomic system activity and a lower impact on blood pressure. Thus, they represent the safest class-particularly among elderly and cardiovascular patients. Serotonin-norepinephrine reuptake inhibitors, particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system. The norepinephrine reuptake inhibitor reboxetine is considered a safe option because of its neutral effects on blood pressure in long-term studies, even if both hypotensive and hypertensive effects are reported. The dopamine-norepinephrine reuptake inhibitor bupropion can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension, especially in patients with cardiovascular diseases. The norepinephrine-serotonin modulators, mirtazapine and mianserin, have minimal effects on blood pressure but may rarely lead to orthostatic hypotension and falls. These adverse effects are also observed with the serotonin-reuptake modulators, nefazodone and trazodone, but seldomly with vortioxetine and vilazodone. Agomelatine, the only melatonergic antidepressant drug, may also have limited effects on blood pressure. Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine. Oral monoamine-oxidase inhibitors, less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis due to ingestion of tyramine-containing food (i.e., cheese reaction). Lastly, a hypertensive crisis may complicate antidepressant treatment as a part of the serotonin syndrome, also including neuromuscular, cognitive, and autonomic dysfunctions. Clinicians treating depressive patients should carefully consider their blood pressure status and cardiovascular comorbidities because of the effects of antidepressant drugs on blood pressure profiles and potential interactions with antihypertensive treatments.
PubMed: 34414219
DOI: 10.3389/fcvm.2021.704281 -
Nature Communications Jun 2021Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine...
Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity. MAOI treatment induces TAM reprogramming and suppresses tumor growth in preclinical mouse syngeneic and human xenograft tumor models. Combining MAOI and anti-PD-1 treatments results in synergistic tumor suppression. Clinical data correlation studies associate high intratumoral MAOA expression with poor patient survival in a broad range of cancers. We further demonstrate that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphoma; Melanoma; Mice; Mice, Inbred C57BL; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neoplasms; Ovarian Neoplasms; Programmed Cell Death 1 Receptor; RNA-Seq; Reactive Oxygen Species; Single-Cell Analysis; T-Lymphocytes; Tumor-Associated Macrophages; Xenograft Model Antitumor Assays
PubMed: 34112755
DOI: 10.1038/s41467-021-23164-2 -
Psychopharmacology Bulletin May 2022This review article features comprehensive discussions on the dietary restrictions issued to patients taking a classic monoamine oxidase inhibitor (phenelzine,... (Review)
Review
This review article features comprehensive discussions on the dietary restrictions issued to patients taking a classic monoamine oxidase inhibitor (phenelzine, tranylcypromine, isocarboxazid), or high-dose (oral or transdermal) selegiline. It equips doctors with the knowledge to explain to their patients which dietary precautions are necessary, and why that is so: MAOIs alter the capacity to metabolize certain monoamines, like tyramine, which causes dose-related blood pressure elevations. Modern food production and hygiene standards have resulted in large reductions of tyramine concentrations in most foodstuffs and beverages, including many cheeses. Thus, the risk of consequential blood pressure increases is considerably reduced-but some caution remains warranted. The effects of other relevant biogenic amines (histamine, dopamine), and of the amino acids L-dopa and L-tryptophan are also discussed. The tables of tyramine data usually presented in MAOI diet guides are by nature unhelpful and imprecise, because tyramine levels vary widely within foods of the same category. For this reason, it is vital that doctors understand the general principles outlined in this guide; that way, they can tailor their instructions and advice to the individual, to his/her lifestyle and situation. This is important because the pressor response is characterized by significant interpatient variability. When all factors are weighed and balanced, the conclusion is that the MAOI diet is not all that difficult. Minimizing the intake of the small number of risky foods is all that is required. Many patients may hardly need to change their diet at all.
Topics: Diet; Female; Humans; Male; Monoamine Oxidase Inhibitors; Phenelzine; Tranylcypromine; Tyramine
PubMed: 35721816
DOI: No ID Found -
Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions.International Journal of Tryptophan... 2019Serotonin syndrome (SS) (also referred to as serotonin toxicity) is a potentially life-threatening drug-induced toxidrome associated with increased serotonergic activity... (Review)
Review
Serotonin syndrome (SS) (also referred to as serotonin toxicity) is a potentially life-threatening drug-induced toxidrome associated with increased serotonergic activity in both the peripheral (PNS) and central nervous systems (CNS). It is characterised by a dose-relevant spectrum of clinical findings related to the level of free serotonin (5-hydroxytryptamine [5-HT]), or 5-HT receptor activation (predominantly the 5-HT and 5-HT subtypes), which include neuromuscular abnormalities, autonomic hyperactivity, and mental state changes. Severe SS is only usually precipitated by the simultaneous initiation of 2 or more serotonergic drugs, but the syndrome can also occur after the initiation of a single serotonergic drug in a susceptible individual, the addition of a second or third agent to long-standing doses of a maintenance serotonergic drug, or after an overdose. The combination of a monoamine oxidase inhibitor (MAOI), in particular MAO-A inhibitors that preferentially inhibit the metabolism of 5-HT, with serotonergic drugs is especially dangerous, and may lead to the most severe form of the syndrome, and occasionally death. This review describes our current understanding of the pathophysiology, clinical presentation and management of SS, and summarises some of the drugs and interactions that may precipitate the condition. We also discuss the newer novel psychoactive substances (NPSs), a growing public health concern due to their increased availability and use, and their potential risk to evoke the syndrome. Finally, we discuss whether the inhibition of tryptophan hydroxylase (TPH), in particular the neuronal isoform (TPH2), may provide an opportunity to pharmacologically target central 5-HT synthesis, and so develop new treatments for severe, life-threatening SS.
PubMed: 31523132
DOI: 10.1177/1178646919873925