A study of muscarinic receptor heterogeneity with weak antagonists
| Autor: | Simon Gitter, Abraham Fisher, Yona Grunfeld, Sasson Cohen, Marta Weinstock |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Quinuclidines
Superior cervical ganglion Stereochemistry Guinea Pigs In Vitro Techniques Mice Structure-Activity Relationship Ileum Ganglia Spinal Equipotent molar ratio Muscarinic acetylcholine receptor medicine Animals Potency Receptors Cholinergic Receptor Pharmacology Salivary gland Chemistry Oxotremorine Parasympatholytics Ganglionic Stimulants Atropine medicine.anatomical_structure Parasympathomimetics Cats Biophysics Cholinesterase Inhibitors Acetylcholine medicine.drug |
| Zdroj: | European Journal of Pharmacology. 38:131-139 |
| ISSN: | 0014-2999 |
| Popis: | A study of heterogeneity among muscarinic receptors was carried out with new rigid molecules, comprising structures in the fused quinuclidine-valerolactone, quinuclidine-cyclohexenone, quinuclidine-cyclohexanone and quinuclidine-cyclohexane derivatives. These are structurally related to the potent muscarinic agent, 3-acetoxyquinuclidine but substantially different from in it conformation. All proved to antagonize acetylcholine-like activity, but to a different extent in different systems. The equipotent molar ratio with respect to atropine (as 1) was: isolated guinea pig ileum, 10,000-1,000; salivary gland (mouse), 1,000-100; superior cervical ganglion (cat), 100-10; CNS (mouse), approximately 10. It is suggested that the rigid structure induces a three-point constrained fit in the receptor (onium group, hydrophobic moiety and carbonyl group), but that not all muscarinic receptors are capable of responding equally. In this case, receptor specificity of the drug is a direct consequence of its graded departure from the preferred conformation of acetycholine and, therefore, is necessarily associated with partial loss of potency. |
| Databáze: | OpenAIRE |
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