Showing posts with label MAO-A activity. Show all posts
Showing posts with label MAO-A activity. Show all posts

Wednesday, January 13, 2010

Clorgyline an old antidepressant may reverse heart failure....

We know that Clorgyline is an irreversible and selective  inhibitor of monoamine oxidase A (MAO-A) . It is structurally related to pargyline (which is a preferential inhibitor of MAO type B) and when compared the antidepressant activity clorgyline is superior over Pargyline. However the drug is no longer in use in humans


Interestingly, now researchers from Johns Hopkins and other researchers have found in animal experiments that this  antidepressant developed over 40 years ago,  can blunt and even reverse the muscle enlargement and weakened pumping function associated with heart failure. Italian heart experts describes in a dozen key laboratory experiments in rodents how the  clorgyline,  blocks the action of enzyme monoamine oxidase-A (MAO-A) and stops its breakdown of a key neurohormone. Norepinephrine, as it is called, controls the pace of blood pumping and makes the heart pump harder and faster in response to stress.

This result is of great significance because of the fact that this is the first evidence showing how elevated MAO-A activity biochemically drives heart failure and that its dangerous downstream effects can be stalled by drug therapy. Hope this vicious chemical circle of stimulant norepinephrine overload and breakdown, might  offer  a disease blueprint with monoamine oxidase-A as the target for drugs similar to clorgyline to rein in the disease.

As claimed by the lead researcher Dr.Nazareno Paolocci, norepinephrine is not properly stored and released from the nerves directed to the heart, monoamine oxidase-A breaks it down, generating dangerous chemical species in the nerves and the heart muscle. and these toxic free radicals produce the same deleterious effects on heart muscle size and pumping function long observed in heart failure. Though further studies with similar class of compounds is essential  for this initial proof of an important principle, its a good achievement..

More details...