Biomaterial Database

Pharmacological characteristics of indoline derivatives in muscarinic receptor subtypes. 1996

S Adachi, and K Koike, and I Takayanagi

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

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.

UI	MeSH Term	Description	Entries
D007082	Ileum	The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297	Male		Males
D008455	(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride	A drug that selectively activates certain subclasses of muscarinic receptors and also activates postganglionic nicotinic receptors. It is commonly used experimentally to distinguish muscarinic receptor subtypes.	McN A-343,McN-A-343,McN-A343,McNeil A 343,A 343, McNeil,McN A 343,McN A343,McNA343
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010880	Piperidines	A family of hexahydropyridines.
D010890	Pirenzepine	An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.	Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D011976	Receptors, Muscarinic	One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.	Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine