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A new and innovative MAOI

Posted by ed_uk on December 24, 2005, at 19:16:26

Hi all,

OK, I've just consumed (more than) a few units of alcohol so this might not be as coherent and it could have been. Anyway, I'm sure you'll let me off given the circumstances :-)

LADOSTIGIL is a *very* interesting drug. It's currently in phase II trials for Alzheimer's disease. It was created by 'blending' the molecular characteristics of rivastigmine (Exelon) with those of rasagiline (Azilect). Rivastigmine (Exelon) is a cholinesterase inhibitor which is used to treat Alzheimer's disease. Rasagiline is an MAO-B inhibitor which is used to treat Parkinson's disease. Rasagiline was recently approved in Europe. It is believed to be neuroprotective as well as offering symptomatic relief.

The result, ladostigil, is a 'brain selective' MAOI and cholinesterase inhibitor. At therapeutic doses, it inhibits both MAO-A and MAO-B in the brain. Inhibition of both forms of MAO is probably necessary to gain a 'robust' antidepressant effect. Ladostigil is particularly interesting because of its alleged 'brain selectivity'. Unlike the classical MAOIs ie. Nardil and Parnate, ladostigil has relatively little effect on the MAO enzymes in the liver and gut. As a result, the risk of a tyramine-induced hypertensive crisis should be much reduced. Although ladostigil *does* potentiate the pressor effect of tyramine, the effect it minimal and no greater than that observed with moclobemide (Manerix/Aurorix). A strict low-tyramine diet is not necessary with moclobemide.

As well as inhibiting MAO-A and MAO-B, ladostigil is a cholinesterase inhibitor (think Aricept). Cholinesterase inhibitors are used in the treatment of Alzheimer's disease to enhance cognition and memory. Unfortunately, they do at times aggravate depression. Ladostigil is not expected to aggravate depression. Even so, if ladostigil was being used 'off label' as an antidepressant, as opposed to a treatment for Alzheimer's disease, it might be necessary (in some cases) to combine it with an anticholinergic - to offset the effects of potentially excessive synaptic levels of acetylcholine. There are many anticholinergics to choose from eg. Cogentin, Artane, Akineton, Kemadrin etc.

Ed


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poster:ed_uk thread:591969
URL: http://www.dr-bob.org/babble/20051221/msgs/591969.html