A new concept in the relationship between biochemical reaction mechanisms and molecular basis of agranulocytosis.
The report of a recent fatality due to agranulocytosis provoked an examination of the plausible mechanisms of neutropenia and agranulocytosis. Drugs which were known to have caused agranulocytosis were used for the investigation. These drugs were aminopyrine, dipyrone (novalgin), phenylbutazone (butazolidin), chlorpromazine, promazine, and chloramphenicol. Mechanisms postulated were (1) generation of RN+ (electrophile) from each of these drugs; (2) interaction of RN+ with protein; (3) interaction of RN+ with DNA and RNA and, (4) formation of antibody to neutrophils due to RN+ interactions. Investigations from contemporary knowledge revealed that the mechanism of RN+-neutrophil interaction was the most plausible, the most convincing, and the most compatible with destruction of neutrophils found in agranulocytosis.
D000380:Agranulocytosis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D000632:Aminopyrine / Q000009:adverse effects; D001323:Autoantibodies / Q000096:biosynthesis; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D002701:Chloramphenicol / Q000009:adverse effects; D002746:Chlorpromazine / Q000009:adverse effects; D004247:DNA / Q000096:biosynthesis; D004177:Dipyrone / Q000009:adverse effects; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010653:Phenylbutazone / Q000009:adverse effects; D011395:Promazine / Q000009:adverse effects; D011485:Protein Binding; D012313:RNA / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014166:Transferases / Q000378:metabolism
D001323:Autoantibodies; D001798:Blood Proteins; D000632:Aminopyrine; D012313:RNA; D004177:Dipyrone; D002701:Chloramphenicol; D004247:DNA; D014166:Transferases; D010653:Phenylbutazone; D011395:Promazine; D002746:Chlorpromazine