Summary
Alinidine (ST 567, N-Allyl-Clonidine) exerted concentration-dependent negative chronotropic effects in isolated, spontaneously-beating sinus node cells and Purkinje fibres of guinea pigs and in ventricular strips of chick embryonic myocardium. Reduction of beat frequency by 30% was found after addition of 8.6 μmol/l alinidine in the former. A chronotropic effect was not seen during Ba2+-induced automaticity or triggered activity in guinea-pig papillary muscles and in enzymatically disaggregated cells of embryonic chick myocardium, which lose the β-adrenoceptor responsiveness of the intact embryonic ventricle. In contrast to alinidine, D 600 showed very pronounced and quinidine minor negative chronotropic effects in these latter experiments. Reduction of excitability, rate of rise of the action potential and velocity of repolarization as well as prolongation of the refractory period were seen after applications of very high concentrations of alinidine (285 μmol/l). In electrically-driven atria isometric peak tension was only slightly changed (increased by 85.5 μmol/l, decreased by 285 μmol/l) but it was reduced (to 36.8%) by alinidine (85.5 μmol/l) in papillary muscles. Both in atria and in papillary muscles, the maximum rate of rise of the action potential was unchanged by alinidine up to 85.5 μmol/l and the slight reduction following 285 μmol/l alinidine application was independent of the rate of stimulation. The present findings confirm the selectivity of the bradycardic effects of alinidine which has a main mode of action different to that of membrane stabilizing compounds or inhibitors of the slow inward current.
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Supported in part by the Austrian Research Fund (2936)
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Tritthart, H.A., Windisch, H. & Heuberger, S. The effects of the bradycardia-producing compound alinidine on action potentials and tension development in cardiac fibres. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 172–177 (1981). https://doi.org/10.1007/BF00505313
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DOI: https://doi.org/10.1007/BF00505313