MadSci Network: Neuroscience

Re: How do monoamine oxidase inhibitors such as moclobemide deactivate MAO?

Date: Fri May 12 17:58:08 2000
Posted By: Amanda Kahn, Grad student, neuroscience, UCSF
Area of science: Neuroscience
ID: 956631527.Ns

Hi Chris!

Moclobemide is one of a newer class of monoamine oxidase (MAO) inhibitors 
called RIMAs, or Reversible Inactivators of MAO-A.   It is used as an 
antidepressant, with fairly good results.

Newer MAOi compounds are selective for either MAO-A or MAO-B, which are 
encoded by distinct genes on the human X chromosome.  MAO-A is responsible 
principally for the deamination of norepinephrine and serotonin, while MAO-B 
deaminates phenylethylamine.  Both enzymes can deaminate dopamine, as well.  
By inhibiting the conversion of  neurotransmitters to their metabolites, 
MAOi compounds increase their availability at the synapse.  If more 
neurotransmitter is present at the synapse (or if it is around longer), then 
signaling to the postsynaptic neuron is increased.   On a side note, 
antidepressants such as Prozac (fluoxetine) have a similar result, but by a 
different mechanism -- these "selective serotonin reuptake inhibitors" or 
SSRIs prevent the re-internalization (rather than metabolism) of serotonin 
by a transporter protein.

Older MAO inhibitors inactivated both MAO-A and MAO-B enzymes, leading to a 
variety of troublesome side effects.  Chief among these was the 
provocatively-named "cheese effect."  MAO breaks down a substance called 
tyramine, which is found in a variety of foods (cheese, risen breads, red 
wine).  MAOi compounds prevented the metabolism of tyramine in the gut; 
increased tyramine levels led, in some cases, to dangerously high blood 
pressure levels.   Furthermore, older MAOi compounds irreversibly 
inactivated MAO in a stoichiometric fashion.  Thus, their activity persisted 
for days and days.  RIMAs, in contrast, have an activity that lasts for 12 
hours or so -- good news if a patient needs to be switched to a different 
class of drug.

Hope this helps,

Amanda Kahn


Here are a few other resources to consult, if you'd like to pursue this 
question further:

Technical information on moclobemide is found here:

A variety of reviews on MAOi compounds  have been published over  the last 
few years.  To see them all, you can do a free search of MEDLINE at the 
National Center for Biotechnology Information's (NCBI) PubMed site:  

Or, many abstracts from recent reviews (including those which I consulted to 
write this answer) have been collected at this site:

For more general information about synaptic transmission and antidepressant 
compounds, try consulting a good neuroscience textbook (such as Kandel's 
Principles of Neuroscience or Purves' Neuroscience).

Or, try this primer on synaptic transmission:

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