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. 1989 Sep;98(1):259–267. doi: 10.1111/j.1476-5381.1989.tb16890.x

The pharmacological evaluation of LY 170680, a novel leukotriene D4 and E4 antagonist in the guinea-pig.

J R Boot 1, A Bond 1, R Gooderham 1, A O'Brien 1, M Parsons 1, K H Thomas 1
PMCID: PMC1854672  PMID: 2553189

Abstract

1. This paper describes the evaluation of LY170680 (5-less than 3-[2(R) (carboxyethylthio)-(S)-hydroxypentadeca 3(E)5(Z)-dienyl]phenyl greater than 1H tetrazole, as an antagonist of the cysteinyl leukotrienes C4, D4, E4, in a variety of in vitro and in vivo models. 2. In vitro, LY170680 was a potent, selective, and competitive antagonist of LTD4, and LTE4. It produced a concentration-dependent rightward displacement of the concentration-response curves elicited by either LTD4 or LTE4 on both the guinea-pig ileal and tracheal preparation. The pA2 values for LY170680 were estimated to be 8.1 +/- 0.2 (n = 8) and 8.1 +/- 0.1 (n = 6) on trachea, and 8.7 +/- 0.1 (n = 12) and 9.0 +/- 0.3 (n = 6) on ileum for both LTD4 and LTE4 respectively. The slopes of the Schild plots in these studies were all close to unity. 3. LY170680 was shown to be a modest antagonist of the LTC4-induced responses on guinea-pig ileum (pA2 7.0 +/- 0.2 n = 5), but had no discernable effects against contractions induced by histamine, prostaglandin E2 (PGE2), PGF2 alpha or acetylcholine. The compound also reduced the LTC4-induced responses on trachea, but in a non competitive manner. 4. Intravenous LY170680 reduced in a dose-dependent manner (ED50 3.8 mg kg-1, 60 min pretreatment) the fall in compliance in the anaesthetized guinea-pig, and the rise in total pulmonary resistance (TPR) (ED50 2.0 mg kg-1, 30 min pretreatment) in the artificially ventilated guinea-pig, produced by intraveous LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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