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 em-
ployed antimuscarinic agents was studied, on the acetylcholine (Ach) induced con-
traction 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-amino-

ethylester 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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