TY - JOUR
T1 - A new probe for heterogeneity in muscarinic receptors
T2 - 2-methyl-spiro-(1,3-dioxolane-4,3′)-quinuclidine
AU - Fisher, Abraham
AU - Weinstock, Marta
AU - Gitter, Simon
AU - Cohen, Sasson
N1 - Funding Information:
Dr. Y. Grunfeld for advice. This work was partly supported by a grant from the Chief Scientist, Ministry of Health.
PY - 1976/6
Y1 - 1976/6
N2 - 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.
AB - 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.
KW - Central muscarinic stimulant
KW - Ganglionic muscarinic stimulant
KW - Muscarinic receptor heterogeneity
KW - Spiro-(dioxolane)-quinuclidine
UR - http://www.scopus.com/inward/record.url?scp=0017122737&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(76)90041-8
DO - 10.1016/0014-2999(76)90041-8
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AN - SCOPUS:0017122737
SN - 0014-2999
VL - 37
SP - 329
EP - 338
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -
