A new probe for heterogeneity in muscarinic receptors: 2-methyl-spiro-(1,3-dioxolane-4,3′)-quinuclidine

Abraham Fisher, Marta Weinstock, Simon Gitter, Sasson Cohen

Research output: Contribution to journalArticlepeer-review

Abstract

The title compound (MSDQ) is a new muscarinic agonist related to 3-acetoxyquinuclidine (3-AcQ) but also of a highly rigid structure. In view of this, it may constitute a probe for the detection of heterogeneity among muscarinic receptors. Indeed, equipotent molar ratios (EPMR) for ACh, 3-AcQ and MSDQ were as follows: guinea pig ileum, 1 : 14 : 240; vasodepressor effect in the cat, 1: 6 : 188. But EPMR for 3-AcQ and MSDQ as stimulants of the superior cervical ganglion in the cat were 1 : 1 and for the induction of tremors in mice 9 : 5. No such subtle differences in receptor specificity were detected when the probe used was the 2,2-diphenyl analogue (DiPSDQ) of MSDQ which was a poerful competitive antagonist in all systems, more potent than atropine, but with a CNS/PNS activity of 1.1 compared to 26 for atropine. In view of this, the use of potent antagonists as probes for muscarinic receptor heterogeneity is questionable.

Original languageEnglish
Pages (from-to)329-338
Number of pages10
JournalEuropean Journal of Pharmacology
Volume37
Issue number2
DOIs
StatePublished - Jun 1976

Keywords

  • Central muscarinic stimulant
  • Ganglionic muscarinic stimulant
  • Muscarinic receptor heterogeneity
  • Spiro-(dioxolane)-quinuclidine

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