ISSN:
1432-1912
Keywords:
Acetylcholine receptors (heart)
;
Acethlcholine receptors (ileum)
;
Muscarinic receptors (heart)
;
Muscarinic receptors (ileum)
;
Neuromuscular blockers on muscarinic receptors
;
Alcuronium
;
Decamethonium
;
Gallamine
;
Pancuronium
;
Ritebronium
;
Tercuronium
;
d-Tubocurarine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. Neuromuscular blocking drugs have a high affinity for muscarinic acetylcholine receptors in the heart atria and ileal smooth muscle. In experiments on homogenates, alcuronium, gallamine, pancuronium, tercuronium and ritebronium inhibited the binding of the muscarinic antagonist (3H)quinuclidinyl, benzilate (QNB) to rat heart atria with IC50 values of 0.15–0.53 μmol · l−1 and to ileal longitudinal muscles with IC50 values of 0.12–0.45 μmol · l−1. d-Tubocurarine and decamethonium inhibited (3H)QNB binding to these tissues with IC50 values of 6.2–8.5 μmol · l−1. 2. For each neuromuscular blocking drug, the IC50 values were virtually identical for (3H)QNB displacement in the homogenates of the atria and of the ileal muscle. 3. Alcuronium and gallamine differed from the other blocking agents in that they produced less steep (3H)QNB displacement curves both in the atria and the ileal muscle; Hill coefficients for the binding of alcuronium and gallamine to atrial and ileal homogenates were lower than unity. 4. On isolated atria, gallamine, pancuronium, ritebronium and tercuronium antagonized the inhibition of tension development caused by the muscarinic agonist, methylfurmethide, with K d values which were of the same order of magnitude as the IC50 values for the displacement of (3H)QNB binding to homogenates; the K d of alcuronium was 12.5 times higher. d-Tubocurarine and decamethonium did not antagonize the effects of methylfurmethide at concentrations up to 100 μmol · l−1. 5. On isolated ileal longitudinal muscle, gallamine and pancuronium antagonized the effects of methylfurmethide with K d values that were 53 times and 100 times higher than their respective K d values in the atria. Alcuronium, d-tubocurarine and decamethonium at concentrations of up to 100 μmol · l−1 did not antagonize the effects of methylfurmethide. Pharmacologically determined K d values of gallamine and pancuronium were 129 times and 83 times higher in the isolated ileal muscle than were their respective IC50 values for (3H)QNB displacement in ileal homogenates. 6. The results indicate that there is a high degree of cardioselectivity in the antimuscarinic action of gallamine, pancuronium and alcuronium, whilst with ritebronium and tercuronium there is little difference between the action on the atria and ileal muscle. The cardioselectivity of gallamine, pancuronium and alcuronium is in a sharp contrast to their equal binding to the homogenates of the atria and ileal smooth muscle. The discrepancy between the binding and pharmacological effect in the ileum suggests that, at low concentrations, gallamine, pancuronium and alcuronium bind to muscarinic receptors in the ileal smooth muscle in such a way that they interfere with the binding of (3H)QNB but not with that of methylfurmethide; the same applies to the binding of d-tuborurarine and decamethonium to muscarinic receptors both in the atria and the ileum. An alternative possibility is that the affinity of muscarinic receptors for neuromuscular blockers is low in intact smooth muscle cells but increases strongly after homogenization.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00501209
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