Summary
The antimuscarinic actions of himbacine were compared with those of atropine and/or homatropine on atria, ileum and trachea from guinea-pigs and rat uterus preparations.
-
1.
The antagonism of acetylcholine or carbachol by all the antagonists was competitive on the preparations studied. The pA2 values of himbacine in all smooth muscle preparations were similar )around 7.2) whereas in atria it exhibited about 10-fold higher affinity (pA2=8.2).
-
2.
In contrast, both atropine and homatropine had similar affinities for muscarine receptors (pA2 values around 9.1 and 7.2 respectively) in both atria and smooth muscle.
-
3.
It may be concluded from these results that cardiac and smooth muscle muscarine receptors are not homogeneous and that himbacine is a relatively potent and selective antagonist for cardiac receptors.
-
4.
The cardio-selectivity of himbacine supports the concept of heterogeneity of muscarine receptors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
Barlow RB, Berry KJ, Glenton PAM, Nikolaou NM, Soh KS (1976) A comparison of affinity constants for muscarinic sensitive acetylcholine receptors in guinea-pig atrial pacemaker cells at 29°C and in ileum at 29°C and 37°C. Br J Pharmacol 58: 613–620
Barnett A, Benforado JM (1966) The nicotinic effects of choline esters and of nicotine in guinea-pig atria. J Pharm Exp Ther 152:129–136
Birdsall NJM, Hulme EC (1983) Muscarinic receptor subclasses. Trends Pharmacol Sci 4:459–463
Brown BR, Crout JR (1970) The sympathomimetic effect of gallamine on the heart. J Pharm Exp Ther 172:266–273
Choo LK, Mitchelson F (1978) Antagonism of cholinomimetics by troxypyrrolidinium in guinea-pig atria and longitudinal ileal muscle: comparison with hemicholinium-3. Eur J Pharmacol 52:313–322
Edinburgh Staff (1970) Pharmacological experiments on isolated preparations, 2nd edn. Churchill Livingstone, Edinburgh p 95
Li CK, Mitchelson F (1980) The selective antimuscarinic action of stercuronium. Br J Parmacol 70:313–321
Löffelholz K (1970) Autoinhibition of nicotinic release of noradrenaline from postganglionic sympathetic nerves. Naunyn-Schmiedeberg's Arch Pharmak Exp Pathol 267:49–63
Nedoma J, Dorofeeva NA, Tucek S, Shelkovnikov SA, Danilov AF (1985) Interaction of the neuromuscular blocking drugs alcuronium, decamethonium, gallamine, pancuronium, ritebronium, tercuronium and d-tubocurarine with muscarinic acetylcholine receptors in the heart and ileum. Naunyn-Schmiedeberg's Arch Pharmacol 329:176–181
Ritchie E, Taylor WC (1967) TheGalbulimma alkaloids. In: Manske RHF (ed) The alkaloids, vol. 9. Academic Press, New York, pp 529–543
Stockton JM, Birdsall NJM, Burgen ASV, Hulme EC (1983) Modification of the binding properties of muscarinic receptors by gallamine. Mol Pharmacol 23:551–557
Van Rossum JM (1963) Cumulative dose-response curves. II. Techniques for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn 143:299–330
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Anwar-ul, S., Gilani, H. & Cobbin, L.B. The cardio-selectivity of himbacine: a muscarine receptor antagonist. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 16–20 (1986). https://doi.org/10.1007/BF00633191
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00633191