A new class of antiarrhythmic--defibrillatory compounds.
Ventricular fibrillation (VF) is a major cause of sudden cardiac death in humans. Currently used antiarrhythmic drugs are aimed at preventing initiation of VF by decreasing the incidence of arrhythmias which can lead to VF. This approach today seems to be insufficient. On the basis of reports that VF can terminate spontaneously in various mammals, and even in humans, we propose pharmaceutical enhancement of self-ventricular defibrillation as a new therapeutical approach. Data obtained over the last decade indicate that a high cardiac extraneuronal noepinephrine level during VF facilitates self-defibrillation. Dibenzazepines (tricyclic antidepressants) and phenothiazines elevate norepinephrine level by inhibiting norepinephrine reuptake and were found to exhibit defibrillatory activity. The relationship of chemical structure to defibrillatory activity was studied in a group of dibenzazepine and phenothiazine compounds.
Erez
M
M
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel.
Varon
D
D
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002415:Cats; D002746:Chlorpromazine / Q000494:pharmacology / Q000627:therapeutic use; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use; D003984:Dibenzazepines / Q000494:pharmacology / Q000627:therapeutic use; D004558:Electric Stimulation; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D007488:Iprindole / Q000494:pharmacology / Q000627:therapeutic use; D008376:Maprotiline / Q000494:pharmacology / Q000627:therapeutic use; D008803:Mianserin / Q000494:pharmacology / Q000627:therapeutic use; D016293:Moricizine / Q000494:pharmacology / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D013329:Structure-Activity Relationship; D014268:Trifluoperazine / Q000494:pharmacology / Q000627:therapeutic use; D014693:Ventricular Fibrillation / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D003984:Dibenzazepines; D014268:Trifluoperazine; D008803:Mianserin; D016293:Moricizine; D008376:Maprotiline; C084605:dibenzepin; D007488:Iprindole; D007099:Imipramine; D003891:Desipramine; D002746:Chlorpromazine; D009638:Norepinephrine