Pharmacological characterization of HSR-609, a novel amphoteric antiallergic agent

• Published in: Japanese Journal of Pharmacology Vol. 76; no. suppl.1; p. 165
• Main Authors: Hiraoka, Yasuko, Oshita, Masafumi, Hosotani, Takeo, Watanabe, Yoshmari, Musoh, Keiichi, Ohashi, Tetsuo, Morikawa, Kouji, Nagata, Osamu, Kato, Hideo
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1998
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)40771-3

Pharmacological profile of a novel selective histamine H_1 receptor antagonist, HSR-609 (3-[4-(8-fluoro-5,11dihydrobenz[b]oxepino[4,3-b]pyridin- 11-ylidene)-piperidinoipropionic acid dihydrate) was studied by functional and binding assays. In functional experiment, HSR-609 concentration-dependently antagonized histamine-induced contraction in guineapig aorta with a significant decrease in maximum response. This insurmountable antagonism of HSR609 was perfectly reversed in the concomitant incubation of diphenhydramine, a classical and surmountable histamine H_1 receptor antagonist. Furthermore, diphenhydramine, added after addition of HSR-609, concentration-dependently reversed the depressed maximum response to histamine caused by HSR-609. The inhibitory effect of HSR-609 on the maximum response to histamine was partially reversed after washing. In saturation binding experiment, when the membrane fraction from guinea-pig cerebral cortex was preincubated with HSR-609 before addition of [^^3 H]-pyliramine, HSR-609 significantly reduced B_max value. These results suggest that HSR-609 is a reversible histamine H_1 receptor antagonist and insurmountable antagonism of HSR-609 is due to its slow dissociation from histamine H_1 receptor.