Lack of intrinsic activity and significant subtype selectivity of SR 95639A at muscarinic receptors

A. S. Mohamed, C. Forray, M. H.M. Aly, E. E. El-Fakahany

Research output: Contribution to journalArticlepeer-review

Abstract

We assessed the intrinsic activity of the purported selective muscarinic M1 receptor agonist SR 95639A (morpholinoethyl-amino-3-benzocyclohepta-(5,6-c)-pyridazine) in inducing several receptor-mediated signals. Our results indicate that SR 95639A lacks the ability to activate phosphoinositide hydrolysis in rat cerebral cortex or in Chinese hamster ovary cells transfected with the genes of the muscarinic m1 and m3 receptors. Similarly, this compound did not exhibit intrinsic activity in stimulating muscarinic receptors which inhibit cyclic AMP synthesis and did not suppress acetylcholine release in rat striatum. In addition, SR 95639A did not show a marked selectivity at the level of the ligand recognition site at the muscarinic M1, M2 and M3 receptors, since it bound to these receptor subtypes with equilibrium dissociation constants of 4.6 and 11 μM, respectively.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume227
Issue number2
DOIs
StatePublished - Oct 1 1992

Keywords

  • Acetylcholine release
  • Muscarinic receptor agonists (selective)
  • Muscarinic receptor subtypes
  • Phosphoinositides
  • SR 95639A
  • cAMP

Fingerprint Dive into the research topics of 'Lack of intrinsic activity and significant subtype selectivity of SR 95639A at muscarinic receptors'. Together they form a unique fingerprint.

Cite this