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 language | English |
|---|---|
| Number of pages | 1 |
| Journal | European Journal of Pharmacology: Molecular Pharmacology |
| Volume | 247 |
| Issue number | 2 |
| DOIs |
|
| Publication status | Published - 15 Oct 1993 |
Keywords
- Cerebral cortex
- Cholinoceptor
- Muscarine receptor antagonist
Cite this
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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. / Christopoulos, Arthur; Loiacono, Richard; Mitchelson, Fred.
In: European Journal of Pharmacology: Molecular Pharmacology, Vol. 247, No. 2, 15.10.1993.Research output: Contribution to journal › Comment / Debate › Other › peer-review
TY - JOUR
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.
KW - Cerebral cortex
KW - Cholinoceptor
KW - Muscarine receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=0027453994&partnerID=8YFLogxK
U2 - 10.1016/0922-4106(93)90083-L
DO - 10.1016/0922-4106(93)90083-L
M3 - Comment / Debate
VL - 247
JO - European Journal of Pharmacology: Molecular Pharmacology
JF - European Journal of Pharmacology: Molecular Pharmacology
SN - 0922-4106
IS - 2
ER -