ISSN:
1420-908X
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract LY188695 was evaluated bothin vitro andin vivo in the guinea pig to determine its pharmacologic profile. The compound antagonized histamine-induced contractions of ileum, aorta, and trachea, with pKB values of 9.9, 9.9, and 9.2 respectively. In the lung parenchymal strip, LY188695 caused a rightward shift of the histamine concentration-response curve with a reduction in the maximal response at all antagonist concentrations tested. The reason for this effect is unknown, but it was not due to a nonspecific depressant action of the compound on the parenchyma. Selectivity was shown by its inactivity against leukotriene D4, bradykinin, prostaglandin F2α, acetylcholine, norepinephrine, and serotonin on various guinea pig and rat smooth muscles. Similary, H2 receptor-mediated relaxation of the rat uterus was unaltered by LY188695. Increases in total pulmonary impedance caused by i.v. histamine to anesthetized guinea pigs were reduced by as little as 3 μg/kg given orally 1 hour prior to histamine challenge. In this system, LY188695 was 15 times more potent than chloropheniramine and 100 times more potent than terfenadine. Similar responses elicited by acetylcholine were not antagonized by LY188695. A duration of action greater than 4 hours was observed in this model. Ovalbumin given i.v. to sensitized guinea pigs increased total pulmonary impedance which was markedly decreased after oral administration of 30 or 100 μg/kg LY188695. These results indicate that LY188695 is a very potent antagonist of H1-mediated responses and suggest that this agent might be useful in disease states characterized by an overproduction of histamine.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01965624
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