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BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro.
Br J Pharmacol. 1991 Nov; 104(3):585-90.BJ

Abstract

1. BAY u3405 (3(R)-[[(4-fluorophenyl) sulphonyl]amino]-1,2,3,4- tetrahydro-9H-carbazole-9-propanoic acid) has been evaluated on airway smooth muscle, from a number of species including man, for its thromboxane A2 (TXA2) antagonist activity. 2. BAY u3405 was a potent, and competitive, antagonist of the TXA2-mimetic U46619-induced contractions of human, guinea-pig, rat and ferret airway smooth muscle with pA2 values between 8.0 and 8.9 and with no inherent contractile activity (10(-9)-10(-4) M). 3. The TXA2 antagonist activity of BAY u3405 was stereoselective. Its (S)-enantiomer, BAY u3406, was approximately 50 fold less effective against U46619 on guinea-pig and human airway smooth muscle. 4. BAY u3405 also competitively antagonized contractions of guinea-pig airway smooth muscle induced by prostaglandin D2 (PGD2) or its metabolite 9 alpha, 11 beta-PGF2. On human and ferret airway smooth muscle it abolished contractions induced by PGD2, PGF2 alpha and 16,16-dimethyl-PGE2. 5. A high concentration (10(-6) M) of BAY u3405 had no effect on the contraction, or relaxation, of airway smooth muscle induced by a range of other agonists, nor did BAY u3405 have any effect on other prostanoid receptor types (DP, EP2, FP or IP). 6. BAY u3405, in contrast to some other TXA2 antagonists, is a potent and selective antagonist on a wide range of airways including human. This high affinity, and the oral activity of the compound described elsewhere, suggest it may be an appropriate tool to investigate the role of prostanoids in airway diseases such as asthma.

Authors+Show Affiliations

Bayer U.K. Ltd., Pharma Research, Stoke Poges.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

1839139

Citation

McKenniff, M G., et al. "BAY U3405, a Potent and Selective Thromboxane A2 Receptor Antagonist On Airway Smooth Muscle in Vitro." British Journal of Pharmacology, vol. 104, no. 3, 1991, pp. 585-90.
McKenniff MG, Norman P, Cuthbert NJ, et al. BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro. Br J Pharmacol. 1991;104(3):585-90.
McKenniff, M. G., Norman, P., Cuthbert, N. J., & Gardiner, P. J. (1991). BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro. British Journal of Pharmacology, 104(3), 585-90.
McKenniff MG, et al. BAY U3405, a Potent and Selective Thromboxane A2 Receptor Antagonist On Airway Smooth Muscle in Vitro. Br J Pharmacol. 1991;104(3):585-90. PubMed PMID: 1839139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro. AU - McKenniff,M G, AU - Norman,P, AU - Cuthbert,N J, AU - Gardiner,P J, PY - 1991/11/1/pubmed PY - 1991/11/1/medline PY - 1991/11/1/entrez SP - 585 EP - 90 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 104 IS - 3 N2 - 1. BAY u3405 (3(R)-[[(4-fluorophenyl) sulphonyl]amino]-1,2,3,4- tetrahydro-9H-carbazole-9-propanoic acid) has been evaluated on airway smooth muscle, from a number of species including man, for its thromboxane A2 (TXA2) antagonist activity. 2. BAY u3405 was a potent, and competitive, antagonist of the TXA2-mimetic U46619-induced contractions of human, guinea-pig, rat and ferret airway smooth muscle with pA2 values between 8.0 and 8.9 and with no inherent contractile activity (10(-9)-10(-4) M). 3. The TXA2 antagonist activity of BAY u3405 was stereoselective. Its (S)-enantiomer, BAY u3406, was approximately 50 fold less effective against U46619 on guinea-pig and human airway smooth muscle. 4. BAY u3405 also competitively antagonized contractions of guinea-pig airway smooth muscle induced by prostaglandin D2 (PGD2) or its metabolite 9 alpha, 11 beta-PGF2. On human and ferret airway smooth muscle it abolished contractions induced by PGD2, PGF2 alpha and 16,16-dimethyl-PGE2. 5. A high concentration (10(-6) M) of BAY u3405 had no effect on the contraction, or relaxation, of airway smooth muscle induced by a range of other agonists, nor did BAY u3405 have any effect on other prostanoid receptor types (DP, EP2, FP or IP). 6. BAY u3405, in contrast to some other TXA2 antagonists, is a potent and selective antagonist on a wide range of airways including human. This high affinity, and the oral activity of the compound described elsewhere, suggest it may be an appropriate tool to investigate the role of prostanoids in airway diseases such as asthma. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/1839139/BAY_u3405_a_potent_and_selective_thromboxane_A2_receptor_antagonist_on_airway_smooth_muscle_in_vitro_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-1188&date=1991&volume=104&issue=3&spage=585 DB - PRIME DP - Unbound Medicine ER -