| MadSci Network: Neuroscience |
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, cheers, Amanda Kahn amandak@phy.ucsf.edu ********** Here are a few other resources to consult, if you'd like to pursue this question further: Technical information on moclobemide is found here: http://www.intox.org/pim151.html 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: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed Or, many abstracts from recent reviews (including those which I consulted to write this answer) have been collected at this site: http://www.biopsychiatry.com/moclob.htm 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: http://www.williams.edu/imput/introduction_main.html
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