A new probe for heterogeneity in muscarinic receptors: 2-methyl-spiro-(1, 3-dioxolane-4, 3')-quinuclidine.
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 powerful 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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006224:Cricetinae; D003864:Depression, Chemical; D005727:Ganglia, Spinal / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009184:Mydriatics / Q000494:pharmacology; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010277:Parasympathomimetics / Q000138:chemical synthesis; D010830:Physostigmine / Q000037:antagonists & inhibitors; D011812:Quinuclidines / Q000138:chemical synthesis / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012472:Salivation / Q000187:drug effects; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D014202:Tremor / Q000139:chemically induced
D009184:Mydriatics; D010277:Parasympathomimetics; D011812:Quinuclidines; D011950:Receptors, Cholinergic; D013141:Spiro Compounds; D010095:Oxotremorine; D010830:Physostigmine