Medizinische Universität Graz - Research portal
Selected Publication:
Doods, HN; Entzeroth, M; Ziegler, H; Mayer, N; Holzer, P.
Pharmacological profile of selective muscarinic receptor antagonists on guinea-pig ileal smooth muscle.
EUR J PHARMACOL 1994 253: 275-281.
Doi: 10.1016/0014-2999(94)90202-X
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Co-authors Med Uni Graz
- Holzer Peter
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The present study examined the effects of a series of tricyclic muscarinic receptor antagonists on muscarinic receptors present in the guinea-pig ileum, both in vitro and in vivo. The selectivity profiles of these antagonists and that of atropine were determined by their affinity for cortical muscarinic M1, cardiac M2 and submandibular M3 receptors and for m4 receptors expressed in CHO cells. The compounds pirenzepine, UH-AH 37, AQ-RA 391 and AQ-RA 618 possessed high affinity (pKi 7.94-8.22) for muscarinic M1 receptors. Pirenzepine exhibited the most pronounced muscarinic M1 selectivity. AF-DX 384 and AQ-RA 741 possessed an approximately 10-fold higher affinity for the cardiac muscarinic M2 receptor than AF-DX 116. However, both compounds also exhibited high affinity for muscarinic m4 receptors. High affinity for muscarinic M3 and m4 receptors was observed for UH-AH 37, AQ-RA 391 and AQ-RA 681. The antagonists were then tested for their interaction with the muscarinic receptors which are responsible for the methacholine-induced contraction of longitudinal muscle in vitro, circular muscle in vivo and muscarinic receptors which mediate the distension-evoked ascending reflex contraction of circular muscle in vitro. Compounds showing high affinity for muscarinic M3 receptors (e.g. AQ-RA 618) were the most potent antagonists in the functional experiments. Comparison of the binding displacement data with the functional results indicates that the effects of methacholine on the longitudinal and circular muscle of the guinea-pig ileum were predominantly mediated by muscarinic M3-type receptors. In contrast, the correlation between muscarinic M2 receptor affinity and antagonism of muscarinic receptors in the ileum was very weak.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Binding Sites -
- Guinea Pigs -
- Ileum - drug effects
- In Vitro - drug effects
- Male - drug effects
- Methacholine Chloride - pharmacology
- Muscarinic Antagonists - pharmacology
- Muscle, Smooth - drug effects
- Parasympatholytics - metabolism
- Rats - metabolism
- Rats, Wistar - metabolism
- Receptors, Muscarinic - metabolism
- Research Support, Non-U.S. Gov't - metabolism
- Find related publications in this database (Keywords)
- Muscarinic Receptor
- Ascending Reflex
- Af-DX 116
- Ileum
- Guinea-Pig
- Smooth Muscle
- Intestinal