Studies on the inhibition by chlorpromazine of myotonia induced by ion channel modulators in mouse skeletal muscle.

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Liu SH, Fu WM, Lin-Shiau SY

Studies on the inhibition by chlorpromazine of myotonia induced by ion channel modulators in mouse skeletal muscle.

Eur J Pharmacol. 1993 Jan 26;231(1):23-30.

PubMed ID

7680317 [ View in PubMed

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Abstract

The myotonic activity of mouse soleus and extensor digitorum longus muscles induced by either a combination of K+ channel blockers (4-aminopyridine) and a Cl- channel blocker (9-anthracene carboxylic acid) or a Cl- channel blocker in low Ca2+ (0.25 mM) Krebs or a Na+ channel activator (veratridine) was characterized in this paper. Myotonic activity was characterized by an increase in both the contraction amplitude and contraction duration accompanied by stimulus-related repeated action potentials. The slow soleus and fast extensor digitorum longus muscles appeared to differ in their responses to these ion channel modifiers. Nevertheless, chlorpromazine at a low concentration of 1 microM significantly inhibited all kinds of myotonic activity; it reduced the prolonged contraction duration and attenuated the stimulus-related repeated action potential firing. This depressant action of chlorpromazine was apparently not correlated with inhibition of either calmodulin or phospholipase A2 activity, since the myotonic depressant action of calmodulin inhibitors, such as dibucaine, flunarizine, chlorpromazine, trifluoperazine and diltiazem, was unrelated to their potency in inhibiting the activity of calmodulin or phospholipase A2. However, phosphatidylcholine was found to inhibit the myotonic depressant action of chlorpromazine. It is therefore, tentatively concluded that chlorpromazine interacted with membrane phospholipids, thereby changing membrane ion channel activity and depressing myotonic activity. These findings indicate that chlorpromazine might be useful in the management of clinical myotonia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cinchocaine	Calmodulin	Protein	Humans	Unknown	Inhibitor	Details