The effects of the bradycardia-producing compound alinidine on action potentials and tension development in cardiac fibres.
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 mumol/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 beta-adrenoceptor responsiveness of the intact embryonic ventricle. In contrast to alinidine, D600 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 mumol/l). In electrically-driven atria isometric peak tension was only slightly changed (increased by 85.5 mumol/l, decreased by 285 mumol/l) but it was reduced (to 36.8%) by alinidine (85.5 mumol/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 mumol/l and the slight reduction following 285 mumol/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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001919:Bradycardia / Q000139:chemically induced*; D002118:Calcium / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002642:Chick Embryo; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D009129:Muscle Tonus / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects
D002317:Cardiovascular Agents; D001464:Barium; C022192:alinidine; D003000:Clonidine; D002118:Calcium