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  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Materials and Method
 ::  Results
 ::  Discussion
 ::  Acknowledgements
 ::  References
 ::  Article Figures
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ARTICLE
Year : 1977  |  Volume : 23  |  Issue : 4  |  Page : 168-171

A study of antimuscarinic agents on skeletal muscle of frog


Department of Pharmacology, J.J.M Medical College, Davangere-577004, India

Correspondence Address:
S R.K Acharya
Department of Pharmacology, J.J.M Medical College, Davangere-577004
India
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Source of Support: None, Conflict of Interest: None


PMID: 149861

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 :: Abstract 

Some of the known antimuscarinic agents were studied for their effect on the acetylcholine induced contraction of the super­fused skeletal muscle of frog, All drugs exhibited varying degrees of curarimimetic effect. During recovery from the drug effect, the tissue exhibited an increased sensitivity to the action o f acetyl­choline; in some instances it was immediate, but it was only at very small concentrations.



How to cite this article:
Acharya S R, Rao S. A study of antimuscarinic agents on skeletal muscle of frog. J Postgrad Med 1977;23:168-71

How to cite this URL:
Acharya S R, Rao S. A study of antimuscarinic agents on skeletal muscle of frog. J Postgrad Med [serial online] 1977 [cited 2020 Nov 24];23:168-71. Available from: https://www.jpgmonline.com/text.asp?1977/23/4/168/42745



 :: Introduction Top


During our undergraduate exercises it was observed, that atropine potentiated the ciliary movement in the oesophagus of frog. In very small concentrations, atropine produce; contraction of isolated gut; [8] it also produces slowing of the sino­atrial node at smaller doses and accele­ration at larger doses in human volunteers. [13] The initial slowing of the heart in clinical practice is explained as being due to the probable stimulation of the vagal nuclei. Some of the antimuscarinic agents may have a dual action, and peri­pheral stimulant action of atropine is of little significance except on the heart. [16] Recently, a dual action of alpha adreno­ceptor antagonists, on isolated rat vas deferens has been reported. [17] Hence, the effect of some of the commonly em­ployed antimuscarinic agents was studied, on the acetylcholine (Ach) induced con­traction of superfused skeletal muscle (skm) of frog.


 :: Materials and Method Top


Rectus abdominis muscle of frog was superfused as reported earlier from our laboratory [1] by using the Ringer solution prepared according to Burn. [11] Ach was used as an agonist in 0.5 mcg. concentra­tion. Combination of drugs was used whereever it was not possible to secure pure chemical. Metamizole was included in the study, since it was present as a combination in one of the anticholinergic preparation avafortan used in the present work. Following antimuscarinic prepara­tions were initially dissolved in distilled water, and working solutions were pre­pared in Ringer to contain 0.1, 1, 10 and 100 mcg. in 0.1 ml.

Propantheline bromide.

Isopropamide bromide.

Adiphenine bromide.

Oxyphenonium bromide.

Atropine sulphate IP.

Avafortan, ampoule containing avapy. razone 24 mg. and metamizole 240 mg. in 3 ml.

Epidosine, Ampoule containing Phenyl­ methyl-valerianic acid β-diethyl­-amino-ethylester brommethylate 8mg. and sodium chloride 8 mg/ml. Metamizole ampoule containing 0.5 g/ml.


 :: Results Top


All drugs exhibited varying degree of curarimimetic effect. Propantheline bro­mide was the most potent and me­tamizole was the least potent as curarimimetic agents. [Table 1], com­pares the curarimimetic effect of drugs. Avafortan and metamizole showed a regression in curarimimetic effect at 1 and 10 mcg. concentrations. The effect of metamizole was statistical) significant (p<0.01) compared with the appropriate control, but when compared with effect at 0.1 mcg. it was insignificant (p>0.1). The effect of drugs lasted for 10-30 minutes.

During recovery, the tissue exhibited an increased sensitivity to the action of Ach. In some instances, it was also imme­diate at 0.1 and 1 mcg. concentrations [Figure 1].[Table 1] shows the comparison of potencies of various drugs at different concentrations. The onset of cholinomi­metic effect was unpredictable.


 :: Discussion Top


The actions of atropine are as exten­sive and complex as are the effects of parasympathetic system which it blocks. [19] Besides being a selective antimuscarinic agent, it is also a tremorogen. [9],[18] The curarimimetic effect of atropine was earlier thought to be owing to the less differentiated character of the amphibian muscle [21] It has been shown to affect con­duction at neuromuscular junction, where the receptors are considered to be nico­tinic. [15] Its action is similar to curare on end plate potentials, but at a 2000 times higher concentration both in normal and denervated rat diaphragm. [6] The use of terms "Nicotinic" and "Muscarinic" raise difficulties, [10] and pilocarpine considered to be a muscarinic agent possess nicotinic action . [20] Our results indicate that anti­muscarinic agents possess varying de­grees of antinicotinic action. Metamizole has been reported to possess a direct myo­lytic action on intestinal smooth muscle, and antinicotinic actions on ganglia. [14] It has also exhibited a curarimimetic effect on Skm [Table 1]. The regression in cura­rimimetic effect observed with Avafortan and metamizole is difficult to explain, and a similar effect has been reported with chlorpromazine [2] and quinidine. [3]

Very small concentrations of Atropine, below those needed to block muscarinic receptors, have been shown to stimulate muscarinic receptors and cause contrac­tion of the isolated gut, showing that atro­pine may act as a partial agonist. [3] We have reported, that on the intestinal smooth muscle, where Ach is present as a local hormone, [7] atropine produces graded contractions of intestine in pg concentrations, whereas in ng concentra­tions it blocks its own effect. [4] In the present study, all drugs have produced an unpredictable cholinomimetic effect on Skm, i.e. an immediate effect at 0.1 and 1 mcg. concentrations [Table 1], and a delayed effect during recovery [Figure 1], showing that on skin also the cholinomi­metic effect is a function of low concen­trations.

Thus, our results indicate that the anti­muscarinic agents exhibit a curarimimetic and a cholinomimetic effect on skm.


 :: Acknowledgements Top


Authors gratefully acknowledge the gift of chemicals used in this study, pro­pantheline bromide from M/s. Searle (India) Ltd, Isopropamide bromide from M/s. Smith Kline and French (India) Limited. Adiphenine bromide and Oxy­phenonium bromide from M/s. Ciba­Geigy of (India) Limited. Thanks are due to Dr. H. Gurupadappa, Principal, for his keen interest and encouragement.

 
 :: References Top

1.Acharya, S. R. K. and Govinda Rao, A. R.: Action of Scorpion Venom on Skeletal Muscle and its Antagonism by Drugs.Arogya J. Health Sci. 1: 69-73, 1975.  Back to cited text no. 1    
2.Acharya. S. R. K. and Govinda Rao, A. R.: Action of Chlorpromazine on Skele­tal Muscle of Frog. Curr. Sci. 44: 147-149,1976.  Back to cited text no. 2    
3.Acharya, S. R. K. and Subba Rao: Action of Quinine, Quinidine and Chloroquine on Skeletal Muscle. Arogya J. Health Sci. 2:123-126, 1976.  Back to cited text no. 3    
4.Acharya, S. R. K. and Subba Rao: A Bio­logical basis for the action of Morphine, Pethidine, Atropine and Antihistamines on intestine. Paper presented before the III Southern Regional Conference of the Phar­macological Society of India at Mangalore Oct. 30th and 31st. 1976.  Back to cited text no. 4    
5.Beranek, R. and Vyskocil, F.: The action of Tubocurarine and Atropine on the nor­mal and denervated rat diaphragm. J. Physiol. 188: 53-66, 1567.  Back to cited text no. 5    
6.Beranek, R. and Vyskocil. F.: Effect of Atropine on the Frog Sartorius Neuromus­cular Junction. J. Physiol., 195: 493-503, 1968.  Back to cited text no. 6    
7.Bowman, W. C., Rand, M. J. and West, G. B: "The text-book of Pharmacology." Revised second print. Blackwell Scienti­fic Publications. Oxford, 1966, p. 173.  Back to cited text no. 7    
8.Bowman, W. C., Rand, M, J. and West, G. B.: "The Textbook of Pharmacology." Revised Second Print. Blackwell Scienti­fic Publications, Oxford, 1966, p. 728.  Back to cited text no. 8    
9.Brimblecombe, R. W. and Pindor, R. M.: "Tremors and Tremorogenic Agents." Scientechnica (Publishers) Ltd., Bristol. 1972, p. 53.  Back to cited text no. 9    
10.Burn. J. H.: Do Adrenergic fibres have muscarinic inhibitory receptors? J. Pharm. Pharmac., 26: 212-215, 1974.  Back to cited text no. 10    
11.Burn, J. H.: Practical Pharmacology. Blackwell Scientific Publications, Oxford, 1952, p. 2.  Back to cited text no. 11    
12.Crossland, J.: "Lewi's Pharmacology." 4th Edn. Churchill Livingstone, London, 1971, p. 79-80.  Back to cited text no. 12    
13.Das, G.: JAMA. Abstracts, 234: 9 & 981, 1975.  Back to cited text no. 13    
14.Dhattiwala. A. S.: Effects of Analgin on Isolated smooth muscle preparations. Ind. J. Pharmac. 6: 103-108, 1974.  Back to cited text no. 14    
15.Gage. P. W.: Generation of end plate potentials. Physiol. Rev., 56: 177-247, 1976.  Back to cited text no. 15    
16.Innes, I. R. and Nickerson, M.: Atropine, Scopalamine and related antimuscarinic drugs, in "Pharmacological basis of thera­peutics." Edited by Goodman. L. S. and Gilman, A., Macmillan Publishing Co., INC. New York, Chp. 25. pp. 516-518, 1975.  Back to cited text no. 16    
17.Jurkiewicz, A. and Jurkiewicz, N. H.: Dual effect of alpha adrenoceptor anta­gonists in rat isolated vas deferens. Brit. J. Pharmac., 56: 169-178, 1976.  Back to cited text no. 17    
18.Osol, A.. Pratt, R. and Altschule, M. D.: The United States Dispensatory, J. B. Lippincott Company. Philadelphia, 1967, p. 172.  Back to cited text no. 18    
19.Osol, A. and Pratt, R.: The United States Dispensatory. J. B. Lippincott Company. Philadelphia, 1973, p. 165.  Back to cited text no. 19    
20.Singh, G. S.: Action of Pilocarpine on the rat blood pressure. Ind. J. Physiol. & Pharmac., 19: 227-228, 1975.  Back to cited text no. 20    
21.Tripathi, O. N., Razdan, M. K. and Gupta. I.: Nature of Cholinergic receptors in the Isolated Frog's rectus abdominis muscle. Ind. J. Physiol and Pharmac., 12: 126-128. 1968.  Back to cited text no. 21    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

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