The calcitonin gene-related peptide (CGRP) is an endogenous peptide that is known to be involved in the development of a migraine. CGRP is also present in the human heart, acts via CGRP receptors, and has been shown to increase the force of contraction (FOC) in isolated, electrically driven human atrial preparations (HAP) from adult patients obtained during open-heart surgery. Here, the hypothesis was tested that the positive inotropic effect (PIE) of CGRP could be attenuated by three anti-migraine drugs, namely ubrogepant, erenumab (both CGRP receptor antagonists), and eptinezumab (a CGRP antagonist). CGRP, cumulatively applied at concentrations ranging from 1 to 100 nM, increased the FOC. In the presence of cilostamide, an inhibitor of phosphodiesterase III, CGRP was more potent and effective than in the absence of cilostamide. Furthermore, when 100 nM CGRP was administered, subsequent application of ubrogepant (1 nM), erenumab (2 nM), and eptinezumab (6 nM) led to a reduction of FOC in HAP. In a more effective way, 1 µM carbachol and 1 µM (-)-N