Eosinophil chemotaxis and anterior uveitis from topical dimaprit and nordimaprit

Topical application of the H₂-histamine receptor agonist, dimaprit (S-[4-N,N-dimethylaminopropyl]isothiourea), produced eosinophil chemotaxis into the anterior segment of rabbit eyes only when an H₂-antagonist was co-administered. Nordimaprit (S-[4-N,N-dimethylaminoethyl]isothiourea), a structural homologue of dimaprit that lacked activity at histamine receptors, produced eosinophil chemotaxis whether or not an H₂-antagonist was co-administered. Onset of eosinophil chemotaxis began after 2 or more days of treatment, and was accompanied by corneal edema, opacification,and ocular inflammation. There was no concurrent eosinophilia in the peripheral blood or in the conjunctiva. The response occurred in pigmented and albino rabbit eyes, and was facilitated by prior co-administration of proparacaine eye drops. Another dimaprit homologue without activity at histamine receptors, homodimaprit (S-[4-N,N-dimethylaminobutyl]isothiourea), did not produce eosinophil chemotaxis when applied topically, nor did the H₂-agonists impromidine, histamine, or 4-methylhistamine, whether co-administered with an H₂-antagonist or not. It was concluded that dimaprit and nordimaprit produced a selective eosinophil chemotaxis unrelated to H₁- and H₂-histamine receptor activity. However, the H₂-agonist activity of dimaprit appeared to inhibit this response unless neutralized by an H₂-antagonist. Topical application of dimaprit with an H₂-antagonist or nordimaprit alone may allow large numbers of non-degranulated eosinophils, free of other cell types, to be harvested from the aqueous humor.