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.
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit / Q000031:analogs & derivatives; D004804:Eosinophils / Q000187:drug effects; D005127:Eye Color / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D011430:Propoxycaine / Q000494:pharmacology; D011817:Rabbits; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014606:Uveitis, Anterior / Q000139:chemically induced*
D011970:Receptors, Histamine H2; C025838:nordimaprit; D002927:Cimetidine; C005717:proxymetacaine; D011430:Propoxycaine; D013890:Thiourea; D017259:Dimaprit