Pharmacology

Original Paper

Pharmacological Characteristics of Indoline Derivatives in Muscarinic Receptor Subtypes

Adachi S. · Koike K. · Takayanagi I.

Author affiliations

Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan

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Pharmacology 1996;53:250–258

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 30, 1996
Accepted: July 09, 1996
Published online: June 10, 2008
Issue release date: 1996

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

The present study was designed to investigate which muscarinic receptors the indoline derivatives interact with and also their pharmacological properties. Compounds I and II contracted guinea-pig ileum in a concentration-dependent manner, whereas compounds III-IX behaved as antagonists and Schild plots gave straight lines. 4-DAMP antagonized the contractile responses to compounds I and II, and the pA2 values for 4-DAMP were 8.96 ± 0.23 and 9.09 ± 0.06, respectively. In guinea-pig left atrium, compound I partly inhibited twitch responses, whereas compound II did not have any effect. In rabbit vas deferens, compounds I and II produced inhibitory effects on twitch responses evoked by field stimulation. Pirenzepine antagonized the inhibitory responses of compounds I and II, and the pA2 values for pirenzepine were 7.90 ± 0.13 and 8.12 ± 0.06, respectively. Compound I has about 150-fold higher affinity to M1 receptors than to M3 receptors, while compound II has about 360-fold higher affinity to M1 receptors. Our results indicate that compounds I and II show 7- and 16-fold higher M1 receptor selectivity than McN-A-343, respectively. Therefore, compound II is selective for M1 receptors over M2 or M3 receptors.

© 1996 S. Karger AG, Basel




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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 30, 1996
Accepted: July 09, 1996
Published online: June 10, 2008
Issue release date: 1996

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA


Copyright / Drug Dosage / Disclaimer

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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