Electropharmacological effects of a new dihydropyridine analog on isolated guinea pig papillary muscles and Purkinje fibers. 1986

P A Molyvdas, and N Sperelakis

The effects of a new dihydropyridine, FR-34235, were compared with those of the dihydropyridine, nifedipine, and verapamil on the normal fast action potentials (APs), slow APs, and contractions of guinea pig papillary muscles and Purkinje fibers. FR-34235 (10(-6) M) blocked the contractions of papillary muscles superfused with normal Tyrode solution within 10-12 min. Maximal upstroke velocity (+Vmax) and overshoot of the fast APs were not affected, whereas the AP durations at 50 and 90% repolarization (APD50 and APD90) were shortened. The effects of FR-34235 on the fast APs and contractions were reversed within 10 min on washout. To determine the effects of the calcium antagonists on slow APs, the fast Na+ channels were inactivated by partial depolarization (to approximately -45 mV) by elevated [K]0, and isoproterenol (10(-6) M) or histamine (10(-5) M) was used to induce slow APs on stimulation. Nifedipine (10(-7) M) and verapamil (2 X 10(-6) M) completely blocked the slow APs. FR-34235 depressed (3 X 10(-8) M) and blocked (10(-7) M) the slow APs in a frequency-dependent manner. The effects were reversed by elevated [Ca]0 or washout of the drug. The contractions accompanying the slow APs were depressed and blocked in parallel with the depression of +Vmax. In guinea pig Purkinje fibers, FR-34235 had no significant effect on the fast AP parameters but produced a marked depression of automaticity. FR-34235 also blocked the slow APs of the Purkinje fibers in a frequency-dependent manner; all drug effects were reversed within 10 min on washout.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D010210 Papillary Muscles Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae. Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D011690 Purkinje Fibers Modified cardiac muscle fibers composing the terminal portion of the heart conduction system. Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D004110 Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions. Aldizem,CRD-401,Cardil,Cardizem,Dilacor,Dilacor XR,Dilren,Diltiazem Hydrochloride,Diltiazem Malate,Dilzem,Tiazac,CRD 401,CRD401
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005260 Female Females

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