A drug with a peculiar mode of action is recently making waves across the globe (At least some parts of it !) Basically , when the world was looking for an anti anginal drug without much hemodynamic effects Trimetazidine fitted this slot .While it’s popularity soared in Europe and Japan , the Americans thought there was a need for a similar drug but supposedly different mechanism of action . Thus Ranalozine was born.It is a piperazine derivative.
How does Ranalozine act ?
There are three important actions for Ranlozine ( 4th one a real surprise !)
- Antianginal
- Anti arrhythmic
- Possible lusiotropic effect
- Anti diabetic*
*It is surprising to note Ranalozine was reducing Hb A1 c . This is incidental or a simple statistical fairy tale we do not know !
Anti anginal
- It acts on the late Na ion channel in phase 2 of action potenial .
- This facilitates excess Ca to be removed from the cells by the NA/Ca exchanger
- Calcium exit improves ischemic myocyte’s metabolic performance as cell injury is prevented .
This makes this drug an effective anti anginal.
The MERLIN TIMI 36 in NSTEMI population became a big dampener against the enthusiasm for this drug.But it did not affect much the sale of the drug !
Antiarrhythmic
A drug , which acts on phase 2 Na channel , it is not at all a surprise to have anti arrhythmic properties .
It can reduce phase 2 reentry like EADS
pro-arrhythmic action
Paradoxically by blocking Na channels it stretches the phase 2 and hence QT interval is prolonged
Lusiotropic action
By preventing the calcium from accumulating from the cytosol it has a theoretical ! lusiotropic action.
It is funny , even theoretical action is enough , for many drugs to enter the standard cardiology literature !
What is major advantage of Ranalozine over other drugs ?
It virtually has no hemodyanmic effects .
Unlike other anti-arrhythmic drugs it acts , only if the late Na channels are abnormally active .
(Which is a case during episodes of ischemia .) This prevents QT interval to prolong in normal persons
In spite of all these meaningful actions and less side effects , FDA approval why cardiologists in the back of the mind think this drug is not based on strong scientific principles , and it could simply represent an industry sponsored placebo ?
I do not know the answer to this question , but I do share the same feeling.
Will it succeed the test of time ?
In this context , I recall a famous statement by my professor “A drug , which has least side effects , is very unlikely to have any desired effect also”
But with world , taking a commercial avatar a success of a drug lies , not in having a desired action but in how many million packs are ultimately sold in the market. It is akin to a bad movie succeeding phenomenally in box office while a good one lying silently unnoticed
Dr.S.Venkatesan MD 