Clinically potent skeletal muscle relaxants are used primarily for their effects on the central nervous system. But they also have direct effects on muscle contraction that possibly involve Ca2+ channels. We compared the effects of dantrolene, an agent known to have a direct action on vertebrate skeletal muscle, with other substances used as (1) relaxants and (2) antagonists of Ca-dependent excitation-contraction coupling. Isolated intact frog muscle cells were injected with the photoprotein aequorin, and membrane potential changes, intracellular Ca2+ transients, and contractile force were measured. Dantrolene (10(-8) to 10(-5) M) decreased the amplitude of Ca2+ transients, did not affect their rates of decay, and reduced contractile force. We also used an integrated digital-imaging system to record microscopic changes, namely, active shortening in myofibrils and changes in striation spacing. Dantrolene did not increase the time between contraction in myofibrils near the surface compared with myofibrils near the center of a cell. Hence dantrolene does not suppress Ca2+ transients by disturbing current flow in the transverse tubular system. Each of the following actually increased Ca2+ transients and contractile force evoked by action potentials: baclofen (10(-7) to 10(-5) M) less than flordipine (10(-6) M) less than meprobamate (10(-7) to 10(-3) M) less than chlordiazepoxide (10(-5) X 10(-4) M) less than procaine (10(-5) to 5 X 10(-4] less than GABA (10(-5) M) less than D-600 (10(-6) M) less than nylidrin (10(-5) M)--in order of increasing potency. Ca2+ channels in the sarcoplasmic reticulum of intact skeletal muscle are evidently inhibited by dantrolene but not by Ca2+ antagonists.

01 Jan 1988·AtherosclerosisQ2 · MEDICINE

Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits

Q2 · MEDICINE

Article

Author: David Kritchevsky ; Shirley A. Tepper ; David M. Klurfeld

Data relating to the effects of calcium channel blockers on experimental atherosclerosis in rabbits are inconsistent with most studies finding no effect on either serum lipids or atherosclerosis. We have administered flordipine (5, 15 or 45 mg/kg/day) for 10 weeks to rabbits fed 1% cholesterol and 4% corn oil. At no level of treatment was there an effect on serum or liver lipids or on aortic sudanophilia.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipidemias	Preclinical	US	The Wistar Institute of Anatomy & Biology	01 Jan 1988

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