Key result
The positive enantiomer EMD 57033 increased shortening during twitch contractions without increasing peak Ca2+ transient amplitude, likely acting at the actin-myosin interface.
The cardiotonic agent EMD 57033 acts directly at the actin-myosin interface to promote force-generating crossbridge states without altering calcium transients.
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Hypothesis-generating for myofilament-targeted inotropes; leaves open translation to human HF therapy.
Solaro et al. (1993) studied Canine cardiac myocytes and myofilaments. Thiadiazinones (EMD 53998, EMD 57033, EMD 57439) was evaluated on Ca2+ signaling, myofilament response, and actomyosin Mg-ATPase activity. The positive enantiomer EMD 57033 increased shortening during twitch contractions without increasing peak Ca2+ transient amplitude, likely acting at the actin-myosin interface.
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