title: Central alpha receptors and their role in digoxin cardiotoxicity.
abstract: The purpose of this study was to determine the role of alpha receptors in the inotropic and cardiotoxic actions of digoxin. Pentobarbital-anesthetized dogs were pretreated centrally with either prazosin, a selective alpha-1 antagonist, or yohimbine, a selective alpha-2 antagonist. Cardiac rhythm, blood pressure and contractile force were monitored during a 60-min period after pretreatment and during a continuous i.v. infusion of digoxin (2.5 micrograms/kg/min). Both agents, when administered into the lateral ventricle, produced depressant effects on hemodynamic parameters. Yohimbine (100 and 200 micrograms/kg i.c.v.) significantly increased the arrhythmogenic and lethal doses of digoxin in a dose-dependent manner. The protective effects of yohimbine (200 micrograms/kg) were not evident when the drug was given peripherally. Central alpha-1 blockade with prazosin increased the lethal dose of digoxin only at the largest dose (100 micrograms/kg i.c.v.) and its effects may be attributed to nonspecific central activity. BHT-933 (5 micrograms/kg i.c.v.), a selective alpha-2 agonist, enhanced the toxic effects of digoxin by decreasing both the arrhythmogenic and lethal dose of digoxin. These results suggest a central alpha-2 receptor mediation of the cardiotoxic actions of digoxin.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology; D003864:Depression, Chemical; D004077:Digoxin / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D004077:Digoxin; D011224:Prazosin