title: Roles of prostaglandins suggested by the prostaglandin agonist/antagonist actions of local anaesthetic, anti-arrhythmic, anti-malarial, tricyclic anti-depressant and methyl xanthine compounds. Effects on membranes and on nucleic acid function.
abstract: We have recently found that local anaesthetic, anti-malarial, anti-arrhythmic, tricyclic antidepressant and methyl xanthine compounds behave as prostaglandin antagonists at drug concentrations readily attainable in human body fluids. We have also found that various hormones, including prolactin, vasopressin and angiotensin when present in physiological concentrations can be potent stimulators of prostaglandin synthesis. Cortisol has no effect on basal prostaglandin systhesis but in physiological concentrations is able to reverse the effects of other hormones. The drugs are thought to act mainly by interfering with either calcium interactions with membranes, or with cyclic nucleotide synthesis or degradation or with nucleic acid function. We propose that prostaglandins play crucial roles at all three points. The hypothesis leads to new approaches to many aspects of cell regulation, to the functions of many systems, especially the neuromuscular, cardiovascular, renal and respiratory systems. It also has profound implications for drug design and evaluation and for the understanding of many clinical disorders.
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002738:Chloroquine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007424:Intracellular Fluid / Q000502:physiology; D008094:Lithium / Q000494:pharmacology; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D013256:Steroids / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D000962:Antimalarials; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D013256:Steroids; D014970:Xanthines; D002738:Chloroquine; D008094:Lithium; D000242:Cyclic AMP; D002118:Calcium