The actions of cimetidine hydrochloride and mepyramine maleate in rat adjuvant arthritis

Adjuvant arthritis in rats was induced by a single subcutaneous injection of Freund adjuvant into a hind paw. The injected paws' mean volume increased continuously by 80±26% after 6 h (acute local response). The injected paw displayed a biphasic response peaking at day 1–2 decreasing to day 5, then increased to day 14 by 123% while the contralateral non-injected paw showed little increase until day 10 and increased by 42% at day 14. The lateral diameter of both knee-joints also increased biphasically, peaking at day 4, decreasing to day 6, then increasing to day 14 (early and late systemic phase). Mepyramine maleate, 1 mg·kg^?1 (i.p.) daily, suppressed only the early systemic phase by 50%. Daily cimetidine hydrochloride, 1 mg·kg^?1·day^?1, almost completely abolished the inflammatory response in the knee joints up to day 12, while at day 14 the supression was 71%. The increase in mean paw volume was also suppressed by orally administered cimetidine. Intraperitoneal doses of cimetidine (3.5 μmol·kg^?1) totally suppressed paw oedema produced by subplantar injection of histamine (1.8 mM) but had no action on equiactive dose of the specific H₁-agonist, 2-pyridylethylamine. Mepyramine at 3.5 μmol·kg^?1 or greater produced no more than 50% suppression of the histamine response. A component of both adjuvant and histamine-induced responses thus appears to be histamine H₂-receptor mediated.