SR 33805 oxalate

Two types of voltage-gated Ca²⁺ channels (VGCC, Ca_V) are found in most nonexcitable cells, T-type and the L-type Ca²⁺ channels^1-2.

SR 33805, a fantofarone derivative, is a potent Ca²⁺ channel antagonist³. It binds allosterically to the a1-subunit of L-type Ca²⁺ channels (Kd = 20 pM), at a site distinct from other types of blockers⁴. It potently inhibits the Ca²⁺ channel, and hence prevents Ca²⁺ influx, in primary mouse cardiac myocytes cultures with IC₅₀ values ranging from 4.1 to 33 nM⁵.

SR 33805 shows selectivity for vascular smooth muscle, inducing vasorelaxation without producing inotropic or chronotropic effects⁶. It inhibits PDGF-stimulated smooth muscle cell proliferation and the associated rise in intracellular Ca²⁺ concentration with IC₅₀ values of 0.2 µM and 0.3 µM, respectively⁷.

Despite its strong Ca²⁺-antagonistic properties, SR33805 increases cardiac cell contractile activity as a consequence of its Ca²⁺-sensitizing effects. These effects are attributable to both an increase in the maximal Ca²⁺-activated force and a length-dependent Ca²⁺-sensitization³.