![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
DW Snyder, RE Giles, RA Keith, YK Yee and RD Krell
Department of Pharmacology, Stuart Pharmaceuticals, Division of ICI Americas Inc., Wilmington, Delaware.
ICI 198,615 is a representative compound from a new class of peptide leukotriene (LT) receptor antagonists. In isolated guinea pig trachea and parenchymal lung strips, ICI 198,615 demonstrated competitive antagonism of the contractile activity of LTD4 and LTE4 with pA2 values of 10.1 to 9.5, respectively. The compound also appeared to antagonize the contractile activity of LTC4 in guinea pig trachea; however, in the presence of an inhibitor of the metabolism of LTC4 to LTD4, ICI 198, 615 provided a pKB value of 5.3, indicating weak antagonism at the LTC4 receptor. ICI 198,615 was also a potent antagonist of LTC4 and LTD4 in isolated human bronchi and pulmonary veins with pKa values of 9.75 +/- 0.32 to 9.20 +/- 0.24, respectively. When evaluated for activity on a broad variety of non-LT receptors, the compound displayed a minimal selectivity of 6310 and a maximal selectivity of greater than 125,000 for the LTE4 receptor. These in vitro studies indicate that ICI 198,615 is the most potent and selective peptide LT receptor antagonist described to date.
This article has been cited by other articles:
|
|
 |
|
  S. NICOSIA, V. CAPRA, S. RAVASI, and G. ENRICO ROVATI Binding to Cysteinyl-Leukotriene Receptors Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): S46 - 50. [Full Text] [PDF]
|
|
|
|
|
|
B. DAHLEN Treatment of Aspirin-intolerant Asthma with Antileukotrienes Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): S137 - 141. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bannenberg, S.-E. Dahlen, M. Luijerink, G. Lundqvist, and R. Morgenstern Leukotriene C4 Is a Tight-binding Inhibitor of Microsomal Glutathione Transferase-1. EFFECTS OF LEUKOTRIENE PATHWAY MODIFIERS J. Biol. Chem., January 22, 1999; 274(4): 1994 - 1999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. DRAZEN Leukotrienes as Mediators of Airway Obstruction Am. J. Respir. Crit. Care Med., November 1, 1998; 158(2007): S193 - S200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. BERNSTEIN Chemistry and Structure-Activity Relationships of Leukotriene Receptor Antagonists Am. J. Respir. Crit. Care Med., June 1, 1997; 157(6): 220S - 226. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Homer-Vanniasinkam and M. J. Gough The Role of Leukotrienes in Controlling Postischemic Skeletal Muscle Function Vascular and Endovascular Surgery, October 1, 1993; 27(8): 585 - 589. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
