ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Position 5 at the Oxotremorine Skeleton as the Stearing Position for Activity at the Muscarinic ReceptorsSubstitution of the Ch2 group at position 5 of oxotremorine (2) by electronegative atoms like O- or N-atom, or by sterically bulkier groups like methyl, N-formyl, or N-acetyl Changes the pharmacological profile of oxotremorine drastically. The O- and N-analogues were potent but unselective (M1/M2) muscarinic agonists. The methyl analogue ((R)-BOK-1) is a muscarine antagonist which is 10 times more potent on the ganglion cervical superius (pA2 = 9.3) than pirenzepine and is able to distinguish between the ileal and ganglion receptor by a factor of 100. The N-formyl derivative differentiates between the two receptors by a factor of 500 with a potency comparable to pirenzepine. The two M1-selective antagonists have higher affinity to the rat-ganglion receptors compared to the affinity to rat-cortex homogenate. The synthesis and the pharmacological activity of several new oxotremorine analogues are discussed.
Additional Material:
1 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19870700827
