Imidazoline receptors represent the binding sites that have high affinity for compounds containing an imidazol(in)e structure. The functional role of I1/I2-imidazoline receptors in physiological and pathological processes is not yet fully elucidated. The receptors of I1 type are involved in the central control of blood pressure and I2 receptors have been associated with various neurobiological states, including analgesia, depression or neurodegenerative disorders. Recently, many attempts have made to explain the role of imidazoline receptors in pathophysiology of the heart (arrhythmia, ischemia). However, no systematic comparative studies were performed nowadays regarding the effect of imidazole(in)es on imidazoline receptors in isolated rat heart atria. In the our previous experiments we observed that some imidazol(in)e agents, regarded on the base of radioligand studies as imidazoline/α2-adrenergic receptor ligands, exerted positive ino- and chronotropic effects on isolated rat heart atria. Those effects were not fully antagonized neither by idazoxan - the classical I2/I1-imidazoline receptor antagonist nor by yohimbine – the classical α2-adrenoceptor antagonist.
The aim of the study was to determine the effect of selected imidazol(in)es: highly specific I1- (moxonidine, rilmenidine) and I2-receptor (RS 45041-190, BU226) ligands as well as guanabenz having “mixed” affinity for imidazoline/α2-adrenergic receptors on the amplitude and rate of contraction of isolated rat heart atria. To determine the potential engagement of I1/I2-receptors in cardiotropic activities of the compounds studied the two selected antagonists: AGN192403 (imidazoline I1-receptor) and 2BFI (imidazoline I2-receptor) were used the first time. The results obtained lead to the conclusion, that I1-imidazoline receptors are only partly involved in positive inotropic effect of moxonidine and rilmenidine which depend mainly on α2-adrenergic receptors. RS 45041-190, BU226, and guanabenz increase the rate of contraction of the atria acting mostly via imidazoline receptors of I2 type. Moreover AGN192403 and 2BFI could be useful compounds in experimental pharmacology for the determination of I1/I2-receptor selectivity of imidazol(in)e agents in search of potential antiarrhythmic/cardiotropic drugs.

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1. Pharmacological evaluation of interaction of selected imidazol(in)e compounds with alpha2-adrenergic receptor by application of the eye mydriasis model in rats