Abstract
Dexmedetomidine is an approved drug that is chemically related to clonidine. Dexmedetomidine is used to induce sedation and anxiolysis. These therapeutic effects of dexmedetomidine are explained by its agonistic action on brain α 2 -adrenoceptors. We tested the hypothesis that dexmedetomidine like clonidine also stimulated human cardiac atrial H 2 -histamine-receptors. We noted that 10 µM dexmedetomidine increased force of contraction in electrically stimulated (1 Hz) human right atrial preparations (HAP, obtained during open heart surgery). These effects were increased by previously applied cilostamide and slightly attenuated by subsequently applied 10 µM cimetidine but greatly attenuated by 10 µM propranolol or when first 10 µM cocaine was given. After pre-stimulation with histamine, subsequently applied 1 µM dexmedetomidine reduced force of contraction in HAP. In left atrial preparations from mice with cardiac-specific overexpression of H 2 -histamine receptors (H 2 -TG), we noted a positive inotropic effect of 10 µM dexmedetomidine in the presence of 100 nM rolipram that was reversed by cimetidine. In left atrial preparations of wild-type mice, 10 µM dexmedetomidine increased force of contraction in the presence of rolipram which was reversed by subsequently applied 10 µM propranolol and attenuated by pretreatment with 10 µM cocaine. These data indicate a direct cardiac action of dexmedetomidine. Dexmedetomidine can probably, in principle, release endogenous cardiac noradrenaline. Thus, dexmedetomidine can act as a partial agonist at human cardiac H 2 -histamine receptors but its main effect in HAP is the release of endogenous β-adrenergic catecholamines.