FIGURE 2.

Cardiac effects associated with Fingolimod-mediated activation of S1PR₁ and S1PR₃. Fingolimod is phosphorylated by sphingosine kinase 2 (SphK2) to generate Fingolimod-phosphate (Fingolimod) that in turn binds to S1PR₁. However, the sustained stimulation leads to S1PR₁ internalization and degradation and to sphingosine kinase 1 (SphK1) inhibition. These effects are probably related to an impairment of the function of the left ventricle (LV). Moreover, via binding and activation of S1PR₃, Fingolimod can induce bradycardia.