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| Year : 1979 | Volume
: 25
| Issue : 1 | Page : 12-14 |
Dual action of antimuscarinic agents on the intestinal smooth muscle
SRK Acharya1, Subba Rao2
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
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 458737 
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 |
| :: Introduction | |  |
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 | | |
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 | | |
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 | | |
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 | | |
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 | | |
| 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.  |
| 2. | Acharya, S. R. K. and Rao, S.: Dual action of antiparkinson drugs (In press) . |
| 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. |
| 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. |
| 5. | Brimblecombe, R. W. and Pinder, R. M.: "Tremors and Tremorogenic Agents." Scientichnica Publishers, Bristol, 1972,p. 53. |
| 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. |
| 7. | Goodstein, A., Lewis, A. and Sumner, M. K.: "Principles of Drug Action." Harper and Row Publishers, New York,1968, p. 3. |
| 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. |
| 9. | Kottmeier, C. A. and Gravenstein, J. S.: The parasympathomimetic activity of atropine and atropine methyl bromide. Anaesthesiology, 29: 1125-1133, 1968. |
| 10. | Sheth, U. K., Dadkar, N. K. and Kamath, U. G.: "Selected Topics in Experimental Pharmacology." The Kothari Book Depot, Bombay, 1972, p. 225 |
[Figure 1], [Figure 2], [Figure 1a]
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