PT - JOURNAL ARTICLE AU - Agnès Rouleau AU - Holger Stark AU - Walter Schunack AU - Jean-Charles Schwartz TI - Anti-Inflammatory and Antinociceptive Properties of BP 2-94, a Histamine H<sub>3</sub>-Receptor Agonist Prodrug DP - 2000 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 219--225 VI - 295 IP - 1 4099 - http://jpet.aspetjournals.org/content/295/1/219.short 4100 - http://jpet.aspetjournals.org/content/295/1/219.full SO - J Pharmacol Exp Ther2000 Oct 01; 295 AB - BP 2-94 is an azomethine prodrug of (R)-α-methylhistamine [(R)-α-MeHA], a potent and selective histamine H3-receptor agonist. When administered orally to mice BP 2-94 was distributed to various peripheral tissues where it released the active drug. BP 2-94 displayed anti-inflammatory and antinociceptive properties in mice. It dose-dependently inhibited carrageenan-induced paw edema with an ED50 value of 0.17 ± 0.05 μmol/kg (p.o.) and a maximal effect of 47%. It also reduced Freund's complete adjuvant-induced paw edema in preventive as well as in curative fashion. Repeated oral administrations of BP 2-94 reduced the pre-established Freund's complete adjuvant-induced edema with an ED50 value of 5 ± 2 μmol/kg (p.o.) and a maximal effect of 47%. The antiedema effects of BP 2-94 and indomethacin were additive. BP 2-94 was also efficient in reducing cyclophosphamide-induced cystitis in mice: it decreased leukocyte infiltration by 62% and plasma protein extravasation by 73% in urinary bladder. In addition, BP 2-94 displayed antinociceptive activity in the capsaicin-induced licking test via H3-receptor stimulation. Its antinociceptive effect was dose dependent, occurring with an ED50 value of 0.4 ± 0.1 μmol/kg (p.o.) and a maximal reduction of licking duration by 69%. No tolerance to the antinociceptive effect was observed after repeated administration of BP 2-94 for 3 days. These observations with BP 2-94 suggest that H3-receptor agonists might represent a novel class of anti-inflammatory and antinociceptive agents. The American Society for Pharmacology and Experimental Therapeutics