I have problem in understanding what it really means that antagonist is irreversible.

I have an allergy and I stopped to take some drugs because of side effects.
I tried to predict how long does it take to go to the same state as before taking drugs.
I learned about biological half-life of medicines so I could predict how long it will take for drug to stop being active.

But then I read that my antihistamine drug is an irreversible antagonist.
I’ve checked the definition, and if I understand it, this means that the receptors are permanently blocked through some reaction with this antagonist.

The question is:
Does it mean that this cell which receptors are blocked is defective forever?
And side effects will never go away because, in this case, cell needs histamine to work properly?
Or we must wait for the cell to die and be replaced by new cell?

Sorry if my questions are not on appropriate level.

  • Can you please name the specific antihistamine you're referring to?
    – Carey Gregory
    Feb 19, 2016 at 16:36
  • Allergist prescribed me Rupafin (rupatadine) and Milukante (montelukast). I’ve found, now more precisely, that rupatadine is pseudo-irreversible antagonist. It differs from truly irreversible antagonist in that no covalent bond is formed with receptor. Montelukast is leukotriene antagonist but I couldn’t find anything about its reversibility.
    – objc3p0
    Feb 19, 2016 at 19:26
  • I can find nothing in the literature for either drug indicating that their effects are anything other than what I posted in my answer. Both are metabolized and eliminated from the body within hours and there is no mention of an irreversible antagonist effect. If you're convinced such an effect exists, please provide the source where you're finding this information. It's difficult to debate "I read somewhere" information.
    – Carey Gregory
    Feb 20, 2016 at 2:31
  • PDF file: Australian Public Assessment Report for Rupatadine. Search for irreversible word.
    – objc3p0
    Feb 20, 2016 at 10:32

2 Answers 2


It means that the receptors are blocked forever. A cell is a living thing, continuously producing new proteins (including receptors) and recycling old ones. So the cell is not defective forever, it will slowly phase out its blocked receptors and replace them with new ones.

You can read the basics of the way receptors work in textbooks on cell signalling, such as http://www.amazon.com/Cellular-Signal-Processing-Introduction-Transduction/dp/0815342152/. A topic of special interest would be ubiquitination, https://en.wikipedia.org/wiki/Ubiquitin#Ubiquitination.

  • Do you have a source confirming that the receptors are indeed blocked permanently? The effects of antihistamines generally wear off within 4-6 hours and it would be pretty surprising that receptors could be replaced that quickly.
    – Carey Gregory
    Feb 19, 2016 at 16:06
  • Sorry, maybe I was unclear here. I answered about the meaning of the "irreversible antagonist" in principle, and assumed that the OP's information that his drug is an irreversible antagonist is correct. I don't know the different antihistamines well enough to know if it is possible that the drug the OP took is indeed an irreversible antagonist, or if he misunderstood that part. I don't know the half-life of histamine receptors specifically (they probably differ by type too), although I've heard of receptors with half-life of less than a day before.
    – rumtscho
    Feb 19, 2016 at 16:21
  • I'm going to ask the OP to name the drug then because I find it an interesting question and it may well depend on the specific drug.
    – Carey Gregory
    Feb 19, 2016 at 16:35
  • 2
    Indeed, it's a very interesting topic. Note that the cell is a complex system which actively repairs itself, so I think degradation is sped up for at least some types of blocked receptors, but certainly not all. The histamine receptors are G-protein coupled, and I remember dimly that these have a longish lifetime (unblocked) when compared to other receptors? My memory is a bit weak on that.
    – rumtscho
    Feb 19, 2016 at 16:55

I’ve found a quotation that sheds some light on the topic:

The rate of termination of the action of a reversible
antagonist is largely dependent on the half-life of the
drug as well as the rate at which it dissociates from its
receptor: the shorter the half-life, the less time it takes
until the effects of the drug are dissipated. However, the
effects of an irreversible antagonist may persist long after
the drug has been cleared from the plasma. In the case of
phenoxybenzamine, the restoration of tissue responsive-
ness after extensive α-receptor blockade is dependent on
synthesis of new receptors, which may take several days

(Peter D. Bryson: Comprehensive Reviews in Toxicology: For Emergency Clinicians)


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