In contrast to its positive cooperativity with orthosteric agonists, C11 potently decreases agonist-activated β1AR signaling, suppresses the isoproterenol response in isolated cardiomyocytes, and largely prevents the development of spontaneous contractile and Ca2+release events in a model of CPVT. The gene discussed is ADRB1; the disease is catecholaminergic polymorphic ventricular tachycardia.