Binding of the muscarine receptor antagonist heptane-1,7-bis(dimethyl-3'-phthalimidopropyl)ammonium bromide at cholinoceptor sites.
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.
Christopoulos
A
A
School of Pharmacology, Victorian College of Pharmacy (Monash University), Parkville, Victoria, Australia.
Loiacono
R
R
Mitchelson
F
F
D000818:Animals; D001667:Binding, Competitive; D008725:Bis-Trimethylammonium Compounds / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D054833:Isoindoles; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists; D009206:Myocardium / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*
D008725:Bis-Trimethylammonium Compounds; D054833:Isoindoles; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011950:Receptors, Cholinergic; C011268:heptane-1,7-bis(dimethyl-3'-phthalimidopropylammonium); D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; C048593:otenzepad