Moreover, the use of SA4503, a Sig-1R agonist, and Sertraline, a selective serotonin reuptake inhibitor (SSRI) and Sig-1R antagonist, in clinical trials for ischemic stroke and depression in patients with HF illustrate the clinical potential of Sig-1R modulation in CVD [208,209,210,211,212,213,214,215,216]. Here, SIGMAR1 is linked to major depressive disorder.