ANTICONVULSANT EFFECTS OF 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE (DMO)

¹ Department of Pharmacology, University of Utah College of Medicine, Salt Lake City, Utah

The anticonvulsant effects of acutely administered 5,5-dimethyl-2,4-oxazolidinedione (DMO) have been determined in rats and mice. It was found that DMO is an effective antiseizure agent against electroshock-, CO₂- and pentylenetetrazol-induced seizures, although the duration of action of DMO is only about 6 hr and its effects are weaker than the anticonvulsant effects of trimethadione (TMO). Since TMO is converted to DMO by liver microsomes, the clear demonstration that DMO has anticonvulsant properties suggests that some of the anticonvulsant effects caused by the injection of TMO can be due to its metabolite, DMO. Studies of the effects of TMO on electroshock seizure threshold (EST) showed that EST rises rapidly after TMO administration, decreases somewhat within 3 hr and then increases to above normal levels 4 to 6 hr after drug administration. Because hepatectomy abolishes the late rise (at 4-6 hr) without decreasing the early increase in EST, it is clear that the secondary rise in EST is related to some function of the liver such as the metabolism or the extrahepatic biliary circulation of TMO.