title: Electrophysiological effects of CRE-1087 in guinea-pig ventricular muscles.
abstract: 1. The electrophysiological effects of CRE-1087, a new antiarrhythmic drug, were studied in guinea-pig papillary muscles. 2. CRE-1087 (10(-7) M-10(-4) M) produced a concentration-dependent decrease in the action potential amplitude and Vmax of the upstroke without altering the action potential duration or the resting membrane potential. 3. At 5 x 10(-6) M, CRE-1087 produced a 5.0 +/- 1.0% tonic Vmax block and this value was not modified at the different rates of stimulation tested. In the presence of CRE-1087, trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (frequency-dependent Vmax block) which augmented at higher rates of stimulation. At 2 Hz the onset kinetics of the frequency-dependent Vmax block was fitted by a monoexponential function being the K value 0.099 +/- 0.012 AP-1. The time constant for the recovery of Vmax from the frequency-dependent block was prolonged to 18.3 +/- 1.5 s. 4. CRE-1087 (5 x 10(-6) M) did not shift the membrane responsiveness curve. 5. CRE-1087 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mM KCl, which suggested that CRE-1087 did not exhibit class IV (Ca antagonist) antiarrhythmic actions. 6. The slow onset and the slow offset kinetics of frequency-dependent Vmax block during repetitive activity suggested that in guinea-pig ventricular muscle fibres CRE-1087 exhibited class Ic antiarrhythmic actions.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Delpón
authors.forename: C
authors.initials: C
authors.lastname: Valenzuela
authors.forename: O
authors.initials: O
authors.lastname: Pérez
authors.forename: J
authors.initials: J
authors.lastname: Tamargo
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D004983:Ethanolamines; C078161:CRE 1087; D007545:Isoproterenol; D011407:Propane