Opportunities for reversible inhibitors of monoamine oxidase-A (RIMAs) in the treatment of depression

CNS Spectrums ◽  
2012 ◽  
Vol 17 (3) ◽  
pp. 107-120 ◽  
Author(s):  
Christopher T. Lum ◽  
Stephen M. Stahl

Treatment-resistant depression (TRD) may be implicated in 33–57% of depression cases. The currently available effective treatments include electroconvulsive therapy (ECT) or augmentation of serotonin selective reuptake inhibitors (SSRIs) with antipsychotics. ECT and antipsychotics are both associated with safety and tolerability concerns. Depression is hypothesized to result from a dysregulation of monoamine neurotransmitters, although the source of the dysregulation has been unclear. However, recent studies have revealed that an enzyme that degrades the neurotransmitters, known as monamine oxidase-A (MAO-A), may be overactive in patients with depression. Thus, treatments for depression that modulate MAO-A could act upstream relative to current antidepressant treatments. Monoamine oxidase inhibitors (MAOIs) can be highly effective therapeutic agents for depression and some anxiety disorders. Some evidence suggests that MAOIs may act by reversing excessive neurotransmitter depletion within the neuron and the synapse. MAOIs tend to be underutilized in clinical practice, due in part to misinformation and mythology about their dietary and drug interactions. The new class of reversible monoamine oxidase inhibitors (RIMAs) has shown efficacy in depression, with safety and tolerability comparable to SSRIs. This article discusses recent progress in RIMAs toward the treatment of TRD. Dietary and drug interactions of MAOIs will be covered, as well as guidelines for integrating these agents into clinical practice.

MedChemComm ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 1871-1881 ◽  
Author(s):  
Bijo Mathew ◽  
Seung Cheol Baek ◽  
Della Grace Thomas Parambi ◽  
Jae Pil Lee ◽  
Monu Joy ◽  
...  

A series of 13 phenyl substituted thiosemicarbazones (SB1–SB13) were synthesized and evaluated for their inhibitory potential towards human recombinant monoamine oxidase A and B (MAO-A and MAO-B, respectively) and acetylcholinesterase.


1989 ◽  
Vol 155 (S6) ◽  
pp. 38-45 ◽  
Author(s):  
A. J. Cooper

The cheese reaction following use of the irreversible monoamine oxidase inhibitors (MAOIs) began to be reported in the UK with increasing frequency from about 1961. By 1965, the underlying mechanism (tyramine-provoked hypertension) had been essentially elucidated. Thereafter, this potentially severe side-effect could have been largely avoided by the use of fairly simple dietary precautions. Unfortunately, suspicion and fear burgeoned, and both the seriousness and the frequency of risk were dramatically inflated. This was a major factor in the subsequent general disuse of the irreversible MAOIs. Second-generation MAOIs which are selective for monoamine oxidase-A and B are now being synthesised and may eliminate the eventuality of hypertension without special dietary precautions.


CNS Spectrums ◽  
2012 ◽  
Vol 17 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Meghan M. Grady ◽  
Stephen M. Stahl

Despite the fact that monoamine oxidase inhibitors (MAOIs) can be highly effective therapeutic agents for depression and some anxiety disorders, they tend to be underutilized in clinical practice. This is due at least in part to the fact that there is a great deal of misinformation and mythology about their dietary and drug interactions. This article is intended to serve as a guide for clinicians who are not particularly familiar with MAO inhibitors; its aim is to help these clinicians competently integrate these agents into clinical practice when appropriate.


2020 ◽  
Vol 23 (9) ◽  
pp. 898-914
Author(s):  
Nisha A. Rehuman ◽  
Bijo Mathew ◽  
Rakesh K. Jat ◽  
Orazio Nicolotti ◽  
Hoon Kim

Background: Monoamine oxidases (MAOs) play a crucial role during the development of various neurodegenerative disorders. There are two MAO isozymes, MAO-A and MAO-B. MAO-A is a flavoenzyme, which binds to the outer mitochondrial membrane and catalyzes the oxidative transformations of neurotransmitters like serotonin, norepinephrine, and dopamine. Materials and Method: Focus on synthetic studies has culminated in the preparation of many MAOA inhibitors, and advancements in combinatorial and parallel synthesis have accelerated the developments of synthetic schemes. Here, we provided an overview of the synthetic protocols employed to prepare different classes of MAO-A inhibitors. We classified these inhibitors according to their molecular scaffolds and the synthetic methods used. Results: Various synthetic and natural derivatives from a different class of MAO-A inhibitors were reported. Conclusion: The review provides a valuable tool for the development of a new class of various selective MAO-A inhibitors for the treatment of depression and other anxiety disorders.


2009 ◽  
Vol 35 (3) ◽  
pp. 623-631 ◽  
Author(s):  
Joanna S Fowler ◽  
Jean Logan ◽  
Albert J Azzaro ◽  
Robert M Fielding ◽  
Wei Zhu ◽  
...  

2012 ◽  
Vol 9 (10) ◽  
pp. 958-961
Author(s):  
Joana Reis ◽  
Catarina Oliveira ◽  
Nuno Milhazes ◽  
Dolores Vina ◽  
Fernanda Borges

2012 ◽  
Vol 9 (10) ◽  
pp. 958-961 ◽  
Author(s):  
Joana Reis ◽  
Catarina Oliveira ◽  
Nuno Milhazes ◽  
Dolores Vina ◽  
Fernanda Borges

2016 ◽  
Vol 12 (2) ◽  
pp. 115-122 ◽  
Author(s):  
Bijo Mathew ◽  
Githa E. Mathew ◽  
Jerad Suresh ◽  
Gülberk Ucar ◽  
Rani Sasidharan ◽  
...  

1985 ◽  
Vol 146 (6) ◽  
pp. 576-584 ◽  
Author(s):  
C. M. B. Pare

SummaryThe present status of monoamine oxidase inhibitors in the treatment of depression is reviewed. With adequate doses they are effective antidepressants, but dosages have in the past been too low. Provided proper dietary precautions are taken, the incidence of fatality from dietary interactions is very small and should not deter doctors from using these drugs, especially in those depressed patients who do not respond to tricyclic-type antidepressants. The present status of combining monoamine oxidase inhibitors with tricyclics is discussed, as are the newer specific inhibitors particularly clorgyline and deprenyl.


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