Nonionic dimer: development and initial testing of an intrathecal contrast agent.
A nonionic dimer (DL-3-117) containing a novel substituent (D,L amino-threitol) was synthesized and tested as an intrathecal contrast medium. In the complement-mediated assay, the dimer was approximately half as inhibitory of hemolysis as metrizamide or iopamidol. The lethal dose (LD50) in protozoa was 320 mg I/ml for DL-3-117, 96 mg I/ml for metrizamide, and 101 mg I/ml for iopamidol. The intravenous LD50 of DL-3-117 in mice was 26 g/kg, and in rats it was 12.7 g/kg. The effective dose (ED50) of intradiencephalic injection in rats was 219 mg I/kg for DL-3-117, 61.9 mg I/kg for metrizamide, and 154.1 mg I/kg for iopamidol, which are significantly different. A dose of 300 mg I/kg injected into a permanently cannulated lateral ventricle produced neurofunctional deficits with all contrast media except DL-3-117, which scored equal to Ringer's solution. Metrizamide and iopamidol in the same model, adapted for aversion conditioning, induced aversion with 45 mg I/kg, while DL-3-117 did not condition the rats.
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage* / Q000633:toxicity; D004027:Diencephalon / Q000000981:diagnostic imaging; D056890:Eukaryota / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D007278:Injections, Spinal; D007463:Iodobenzoates / Q000008:administration & dosage*; D007479:Iopamidol; D007483:Iothalamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D007928:Lethal Dose 50; D008297:Male; D008793:Metrizamide / Q000008:administration & dosage; D051379:Mice; D011859:Radiography; D051381:Rats; D014283:Triiodobenzoic Acids / Q000008:administration & dosage* / Q000633:toxicity
D003287:Contrast Media; D007463:Iodobenzoates; D014283:Triiodobenzoic Acids; D007483:Iothalamic Acid; C033300:iotrolan; D007479:Iopamidol; D008793:Metrizamide