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Effects of calcium antagonists on mechanical responses of mammalian skeletal muscles
Abstract:
Rodent muscles were exposed to several organic calcium antagonists, and mechanical responses to direct electrical stimulation were recorded. Verapamil and D600, at 25 microM, depressed twitch and tetanus tension and caused fading of the tetanus plateau. These effects increased with frequency of stimulation, and were not reversed by doubled extracellular calcium. Depression of tension progressed to complete paralysis after 60-90 min exposure to verapamil. Bepridil and diltiazem both caused depression of tension and tetanus fade. Nifedipine caused marked, and nitrendipine caused slight, potentiation of twitch tension but did not alter tetanic tension. The magnitude of the observed effects on tension (either depression or potentiation) correlated with neither the relative calcium antagonist potencies of the drugs in other tissues nor with the ability of the drugs to cross the cell membrane. The continued decline in tension observed on prolonged exposure indicates that chronic exposure to low levels in vivo might lead to significant muscle weakness.
Insights
Organic calcium antagonists like verapamil can significantly weaken rodent muscles by reducing tension and causing paralysis. Chronic exposure may lead to muscle weakness in vivo.
Area of Science:
- Pharmacology
- Muscle Physiology
Background:
- Organic calcium antagonists are widely used clinically.
- Their effects on skeletal muscle contractility are not fully understood.
Purpose of the Study:
- To investigate the effects of various organic calcium antagonists on rodent skeletal muscle.
- To determine the relationship between drug properties and observed muscle effects.
Main Methods:
- Rodent muscles were subjected to direct electrical stimulation.
- Mechanical responses (twitch and tetanus tension) were recorded.
- Muscles were exposed to verapamil, D600, bepridil, diltiazem, nifedipine, and nitrendipine.
Main Results:
- Verapamil and D600 depressed twitch and tetanus tension, causing paralysis after prolonged exposure.
- Bepridil and diltiazem also depressed tension and caused tetanus fade.
- Nifedipine and nitrendipine showed varying effects on twitch tension but not tetanic tension.
- Drug effects did not correlate with potency in other tissues or membrane permeability.
Conclusions:
- Organic calcium antagonists have significant, dose-dependent effects on skeletal muscle contractility.
- Prolonged exposure to these drugs can lead to muscle weakness and paralysis.
- Further research is needed to understand the in vivo implications of chronic low-level exposure.