The Effect Of Antimuscurinic Drug On Skeletal Muscle

Year : 1977 | Volume : 23 | Issue : 4 | Page : 168-171

A Study of Antimuscarinic Agents on Skeletal Muscle of Frog S R.K Acharya, Subba Rao 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

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 of acetylcholine; in some instances it was immediate, but it was only at very small concentrations. Introduction 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. Methods 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-aminoethylester brommethylate 8mg. and sodium chloride 8 mg/ml. Metamizole ampoule containing 0.5 g/ml. Results 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 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 [2] [3] has been reported with chlorpromazine and quinidine. 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 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.

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