Electrophysiological effects of alinidine (ST 567) on sinoatrial node fibres in the rabbit heart.
In a study of the electrophysiological effects of alinidine a concentration of 0.7-14.3 mumol X litre-1 decreased the rate of diastolic depolarisation and prolonged especially the terminal part of the action potential in the rabbit sinoatrial node. It did not induce pacemaker shifts since the effects were not restricted to the primary pacemaker or the central nodal area but were evident in the more peripheral nodal region. The substitution of chlorine ions by other anions did not prevent the decrease in the rate of diastolic depolarisation due to alinidine but did prevent the effect on the action potential duration. The decreased chronotropic action of alinidine in low chlorine Tyrode solution was, however, caused by a shift of pacemaker dominance towards an atrial pacemaker. This pacemaker shift concealed the response of the primary pacemaker to alinidine in low chlorine Tyrode. Blockade of the pacemaker current of if by caesium prevented neither the alinidine effect on the diastolic depolarisation completely nor its effect on the action potential duration, but blockade of if probably was one of the determinants of the action of alinidine. It cannot be excluded that alinidine interferes with still another current than if. Alinidine decreased the chronotropic responses to adrenaline and to acetylcholine and also prevented pacemaker shifts due to these substances.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002586:Cesium / Q000494:pharmacology; D002713:Chlorine / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003864:Depression, Chemical; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects*; D013997:Time Factors
D002586:Cesium; D002713:Chlorine; C022192:alinidine; D003000:Clonidine; D000109:Acetylcholine; D004837:Epinephrine