Binding of the muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl) ammonium bromide at cholinoceptor sites. European Journal of Pharmacology - Molecular Pharmacology Section, 246 (1993) 1-8

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Abstract

The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissues. C7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[3H]nicotine and [3H]pirenzepine binding in rat cortex by C7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C7/3-phth in displacement studies using [3H]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed.

Original languageEnglish
Number of pages1
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume247
Issue number2
DOIs
Publication statusPublished - 15 Oct 1993

Keywords

  • Cerebral cortex
  • Cholinoceptor
  • Muscarine receptor antagonist

Cite this

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title = "Binding of the muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl) ammonium bromide at cholinoceptor sites. European Journal of Pharmacology - Molecular Pharmacology Section, 246 (1993) 1-8",
abstract = "The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissues. C7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[3H]nicotine and [3H]pirenzepine binding in rat cortex by C7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C7/3-phth in displacement studies using [3H]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed.",
keywords = "Cerebral cortex, Cholinoceptor, Muscarine receptor antagonist",
author = "Arthur Christopoulos and Richard Loiacono and Fred Mitchelson",
year = "1993",
month = "10",
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doi = "10.1016/0922-4106(93)90083-L",
language = "English",
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journal = "European Journal of Pharmacology: Molecular Pharmacology",
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T1 - Binding of the muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl) ammonium bromide at cholinoceptor sites. European Journal of Pharmacology - Molecular Pharmacology Section, 246 (1993) 1-8

AU - Christopoulos, Arthur

AU - Loiacono, Richard

AU - Mitchelson, Fred

PY - 1993/10/15

Y1 - 1993/10/15

N2 - The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissues. C7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[3H]nicotine and [3H]pirenzepine binding in rat cortex by C7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C7/3-phth in displacement studies using [3H]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed.

AB - The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3′-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissues. C7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[3H]nicotine and [3H]pirenzepine binding in rat cortex by C7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C7/3-phth in displacement studies using [3H]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed.

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