Thrombocytopenia in rats and dogs administered the antidepressant compound MDL-19,660.
Two-week oral administration of MDL-19,660, a triazole antidepressant compound, resulted in a dose-related thrombocytopenia in rats given 40-360 mg/kg/d and dogs treated with 5-50 mg/kg/d. Consumptive loss of platelets was not apparent since splenomegaly, hemorrhage, microscopic thrombi or prolonged coagulation times (prothrombin and activated partial thromboplastin) were not observed. Platelet production did not appear to be impaired since megakaryocytes in the bone marrow of treated animals were similar in number or slightly increased compared to control animals. Although the pathogenesis of this thrombocytopenia is presently unknown, intravascular destruction by immune mechanisms or direct drug-related effects seems most likely.
Yarrington
J T
JT
Toxicology Department, Marion Merrell Dow, Inc., Cincinnati, OH 45215.
Kociba
G J
GJ
Gibson
J P
JP
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002452:Cell Count / Q000187:drug effects; D003863:Depression / Q000139:chemically induced; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*; D014230:Triazoles / Q000008:administration & dosage / Q000633:toxicity*
D000928:Antidepressive Agents; D014230:Triazoles; C065325:MDL 19660