Posts Tagged ‘merlin timi 36’

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 !


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

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