Prostaglandins and the cardiotoxic effects of doxepin in rabbits and guinea-pigs.
Intravenous administration of tricyclic antidepressants to rabbits leads to dysrhythmias largely attributable to their non-specific membrane effects. Further experiments with doxepin (Dx) were conducted to assess an eventual contribution by prostaglandins (PG) to these events. Dx infused intravenously to conscious or anaesthetized guinea-pigs proved as cardiotoxic as amitriptyline but more toxic than protriptyline, thus confirming our previous results in rabbits. PG F2 alpha given intravenously before or during the Dx infusion failed to antagonize cardiotoxicity. In conscious rabbits, pretreatment with drugs (aminophenazon, indomethacin, tolfenamic acid) known to inhibit PG synthesis failed to modify the Dx cardiotoxicity as also did PG F2 alpha which elevated blood pressure, however. PG F2 alpha also failed to counteract the ouabain cardiotoxicity in anaesthetized guinea-pigs and major Ba++-induced dysrhythmias in conscious rabbits. Our results suggest that a) at least Dx induced dysrhythmias are unresponsive to PGs, and that b) previous speculations about PGs as antiarrhythmic agents may be exaggerated.
D000639:Amitriptyline / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D001464:Barium / Q000633:toxicity; D004316:Doxepin / Q000633:toxicity*; D006168:Guinea Pigs; D010042:Ouabain / Q000633:toxicity; D011460:Prostaglandins F / Q000494:pharmacology*; D011530:Protriptyline / Q000633:toxicity; D011817:Rabbits
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011460:Prostaglandins F; D004316:Doxepin; D000639:Amitriptyline; D001464:Barium; D011530:Protriptyline; D010042:Ouabain