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 ::  Abstract
 ::  Introduction
 ::  Material And Methods
 ::  Results
 ::  Discussion
 ::  Acknowledgements
 ::  References
 ::  Article Figures

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Year : 1979  |  Volume : 25  |  Issue : 1  |  Page : 12-14

Dual action of antimuscarinic agents on the intestinal smooth muscle

1 Department of Pharmacology. J.T.M. Medical College, Davengere 577 004, India
2 Professor of Pharmacology, Government Medical College, Bellary-583 102, India

Correspondence Address:
Subba Rao
Professor of Pharmacology, Government Medical College, Bellary-583 102
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Source of Support: None, Conflict of Interest: None

PMID: 458737

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 :: Abstract 

Propantheline, oxyphenonium, isoproponaide, epidosine, adiphe­nine and atropine were studied for their effect on the superfused infesting of guinea pig and rat. In small, concentrations, all drugs produced a contraction, which with increasing concentration, was Hocked. Occasionally, a contraction and a relaxation or vice versa was recorded. A partial antagonism and a potentiation on the action of acetylcholine (Ach) during recovery was observed. In very high concentrations, all drugs produced a graded contraction of intestine, except adiphenine which produced a sustained contraction. Some­ times, a contraction and a relaxation was also observed.

How to cite this article:
Acharya S, Rao S. Dual action of antimuscarinic agents on the intestinal smooth muscle. J Postgrad Med 1979;25:12-4

How to cite this URL:
Acharya S, Rao S. Dual action of antimuscarinic agents on the intestinal smooth muscle. J Postgrad Med [serial online] 1979 [cited 2023 Jun 5];25:12-4. Available from:

 :: Introduction Top

The antimuscarinic drug atropine, ex­hibits a dual action on the intestine, [4] produces an inhibition of the sino-atrial node [6] and an initial inhibition of the heart, which is more marked with scopo­lamine. [8] We reported an unpredictable cholinomimetic effect of antimuscarinic drugs on skeletal muscle, despite their curarimimetic action. [1] A parasympatho­mimetic activity of atropine and atropine methylbromide has been reported and it was suggested that the cardiac slowing was more peripheral than central, since atropine methyl bromide does not cross the blood brain barrier. [9] It has been suggested, that some of the antimuscari­nic drugs may have a dual action. [8] The present study was undertaken to test whether all antimuscarinic drugs exhibit dual action.

 :: Material And Methods Top

Prepared pieces of duodenum, jejunum, and ileum of guinea pigs and rats were superfused by using two unit thermo­static isolated organ bath. The lower inlet of the organ bath was closed. A rubber cork with a hole and a hook in the center was placed inside the organ bath. One end of the intestine was fixed to the hook in the cork, and the other end to the frontal writing lever. The tyrode solution, prepared according to the method described by Sheth et al [10] was diverted from the preheating coil and was made to drop over the thread at a constant rate. The temperature was maintained at 37 ± 1° C. The reservoir was slowly and continuously aerated, The following drugs, dissolved in distil­led water were used in 1 attogram, 1 Femtogram. 1 pg. 1 ng., 1 mcg, 100 mcg, 2C0 mcg. and 4CC mcg. concentrations, in 0.01 ml. volume:

Propantheline Bromide,

Isopropamide Bromide,

Adiphenine Bromide,

Oxyphenonium Bromide,

Epidosine ampoule containing phenyl

methyl valerianic acid-β diethyl

aminoester-brommethylate 8 mg/ml

and sodium chloride 8 mg/ml.

Atropine sulphate.

 :: Results Top

In low concentrations, all drugs pro­duced a contraction of intestine. The contraction was observed at an optimum concentration rather than the lowest. Further increase in concentrations, blocked the contraction and sometimes a relaxation was recorded. Occasionally, a relaxation and a contraction was pro­duced by the same concentration [Figure 1] a. During recovery, a partial antago­nism as well as a potentiation on the ac­tion of Ach was observed [Figure 2]. In very high concentrations (100 mcg and above), all drugs produced a contraction of intestine [Figure l]a and [Figure 2], immediately after which, the tissue was insensitive to Ach. Sometimes, the contraction was noticed at 1 mcg. itself. Adiphenine pro­duced a sustained contraction lasting for 30-40 minutes [Figure 2].

 :: Discussion Top

All drugs have produced a contraction of the instestine in small concentrations. The contraction appears to have been caused by a potentiating effect of these drugs on Ach, present in the smooth muscle as a local hormone, [3] rather than a direct cholinomimetic effect, as these drugs potentiate exegenous Ach on skeletal muscle unpredictably. [1] The con­traction has manifested at an optimum concentration, rather than the lowest [Figure 1a] and [Figure 2], which with increas­ing concentrations is blocked, owing to the manifestation of antimuscarinic effect. Thus, our findings are in agreement with the suggestion, that some of the antimuscarinic drugs may have a dual ac­tion. [8] In our other study, [2] it has been observed, that scopolamine is not only less potent in antagonising Ach on skele­tal muscle, but also produces more num­ber of immediate potentiation of Ach, than atropine. [1] This may explain, why in low doses the cardiac inhibition is greater with scopolamine than with atro­pine. The cardiac slowing may be more peripheral than central, as suggested by the earlier workers, since atropine methyl bromide, which does not cross blood brain barrier also induces cardiac slow­ing. [9] And in the present study, the other quaternery ammonium compounds iso­prapamide, propantheline, and oxypheno­nium have also exhibited a dual action. The dual action of atropine may explain its tremorogenic effect. [5] The relaxation of intestine observed [Figure 1]a may be a direct action, as it is produced occasion­ally in all concentrations and may also be unrelated to the degree of tension de­veloped by the tissue, since both relaxa­tion and contraction are produced at the same concentration [Figure 1]a.

All drugs have produced a graded con­traction of the intestinal smooth muscle at higher concentrations, despite their own antimuscarinic effect; this suggests that the effect is produced by a direct action. Adiphenine. one of the weak antimuscarinic drugs, produces a sustain­ed contraction [Figure 2], which may be due to the involvement of strong bonds in the drug receptor interaction. [7]

 :: Acknowledgements Top

Authors are indebted to the following Pharmaceutical firms for the generous supply of their products, propantheline from M/s. Searle (India) Ltd., Isopropa­mide from M/s. Smith Kline and French (India) Ltd., and Adiphenine and Oxy­phenonium from M/s. Ciba-Geigy of India Ltd., They are grateful to Dr.Gurupadappa, Principal, for his encour­agement.

 :: References Top

1.Acharya, S. R. K. and Rao, S.: A study of antimuscarinic agents on skeletal muscle of frog. J. Postgrad. Med., 23:168-171, 1977.  Back to cited text no. 1    
2.Acharya, S. R. K. and Rao, S.: Dual action of antiparkinson drugs (In press) .  Back to cited text no. 2    
3.Bowman, W. C., Rand, M. J. and West, G. B.: "Text Book of Pharmacology." Revised Second Print., Blackwell Scienti­fic Publications, Oxford, 1966, p. 173.  Back to cited text no. 3    
4.Bowman, W. C., Rand, M. J. and West, G. B.: "'Text Book of Pharmacology"' Revised Second Print., Blackwell Scienti­fic Publications, Oxford. 1966, p. 728.  Back to cited text no. 4    
5.Brimblecombe, R. W. and Pinder, R. M.: "Tremors and Tremorogenic Agents." Scientichnica Publishers, Bristol, 1972,p. 53.  Back to cited text no. 5    
6.Das, G.. Talmers, F. N. and Weissler. A. M.: New observations on the effects of atropine on sino-atrial and atrio-ventri­cular nodes in man. Amer. J. Cardiol.. 36: 281-285, 1975: Abstrated in J. Amer. Med. Assoc., 234: 981, 1975.  Back to cited text no. 6    
7.Goodstein, A., Lewis, A. and Sumner, M. K.: "Principles of Drug Action." Harper and Row Publishers, New York,1968, p. 3.  Back to cited text no. 7    
8.Innes, I. R. and Nickerson, M.: Atropine. Scopolamine, and related antimuscarinic drugs. In, "Pharmacological Basis of Therapeutics." Editors: Goodman, L. S. and Gilman, A., MacMillan Publishing Co. Inc., London, New York, 197.3 Chapter 25. pp. .516-517.  Back to cited text no. 8    
9.Kottmeier, C. A. and Gravenstein, J. S.: The parasympathomimetic activity of atropine and atropine methyl bromide. Anaesthesiology, 29: 1125-1133, 1968.  Back to cited text no. 9    
10.Sheth, U. K., Dadkar, N. K. and Kamath, U. G.: "Selected Topics in Experimental Pharmacology." The Kothari Book Depot, Bombay, 1972, p. 225  Back to cited text no. 10    


  [Figure 1], [Figure 2], [Figure 1a]


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