'H1-antagonist' is a compound formed from the receptor designation 'H1' (the first subtype of histamine receptors, where 'H' stands for histamine and '1' is a numeric subtype label) and 'antagonist' (from Greek 'antagōnistēs' meaning 'opponent' or 'rival').

'antagonist' entered English via Latin and French from Greek 'antagōnistēs' (ἀνταγωνιστής). The use of 'H1' as a label for a histamine receptor subtype arose in the 20th century as pharmacologists classified receptor subtypes; the compound term 'H1-antagonist' developed in biomedical literature to denote drugs blocking that subtype.

Originally 'antagonist' meant 'an opponent' or 'one who struggles against'; in pharmacological contexts it evolved to mean 'a substance that inhibits or blocks the action of a receptor or biological agent,' as in 'H1-antagonist.'