In this publication (PDF) I encountered the following word:

Binding of rupatadine to histamine H1 receptors isolated from the guinea-pig cerebellum and lung was demonstrated by inhibition of 3H-mepyramine binding; equilibrium inhibition constant (affinity) [Ki] values were 26–256 nM in the various experiments. Binding was time-dependent and pseudo-irreversible. Rupatadine was ~7.5 and 10-times more potent than the structurally-related anti-histamines loratadine and fexofenadine. H1 receptor occupation by rupatadine in guinea-pig cerebellum and lung after oral (PO) dosing was relatively rapid (with maximum binding evident at 2–4 hours post-dose) and dose-dependent; low or no binding was seen at 48 hours post-dose.

In this context, what does pseudo-irreversible mean? Since it goes on to say the binding had dissipated within 48 hours, it seems to mean persistent or long-lived. Is that correct or does it have a more specific meaning in biology?


1 Answer 1


it seems to mean persistent or long-lived. Is that correct...?

Yes, it's correct, but how persistent the effect is is related to the rate of dissociation or rate of turnover of the receptor. It is relative, so to speak; relative to the effect of non-irreversible receptor binding.

Irreversible inhibition of, say, a cell surface receptor means that a drug (agonist/antagonist) binds permanently to the target receptor, usually by binding covalently; the chemical reaction is not reversible. This isn't synonymous with a permanent effect on a cell or organism; that depends on turnover of the receptor. A "faulty" receptor may be replaced quite quickly or not; it depends of the cell and the receptor.

Pseudo-irreversible means that the drug acts in a manner similar to irreversibly bound agonists/antagonists, but there is no covalent bond formed; if a drug/molecule which has a sufficiently high affinity for the receptor is introduced (in a sufficiently high quantity), the new molecule will replace that which was strongly bound before (the pseudo-irreversibly bound drug.)

Some of these types of reactions have been studied more than others. One example of this can be seen with h5-HT7 receptors, which are subject to pseudo-irreversible inactivation by risperidone and 9-OH-risperidone.

Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions

  • $\begingroup$ Sigh... why didn't you just answer the question in Health? $\endgroup$ Feb 20, 2016 at 23:28
  • $\begingroup$ @CareyGregory - That wasn't asked on Health, at least not to my understanding. $\endgroup$ Feb 21, 2016 at 0:05

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