Preliminary Toxicity Studies on N,N,N'-Trimeryl-N' (2-Hydrdxyl-3-Methyl-5-Iodobenzyl)-1,3-Propanediamine (HIPDM), A new Brain Perfusion Imaging Agent

Abstract

HIPDM is a promising new agent for use in conjunction with single-photon emission tomography (SPECT) for studying local cerebral perfusion. The acute toxicity of HIPDM was studied in the rat and the rabbit. The LD50 for HIPDM in the rat was 36 mg/kg. Animals displayed signs of CNS involvement in toxicity which included convulsions, and locomotor deficits. The LD50 in the rabbit was approximately 20 mg/kg. Both loss of motor coordination and convulsions were the predominant signs of toxicity. Both the rat and rabbit displayed little individual variation in response to HIPDM as indicated by the steepness of the dose response curves. Repeated administration of HIPDM in the rabbit for two weeks at 1.4 mg/kg/day resulted in no effects on weight gain. Similarly there were no adverse effects on clinical chemistry and hematological parameters in serum and blood. Terminal tissue analysis revealed no induction of histopathological lesions in the brain or other tissues. It is unlikely that acute toxic manifestations will result from doses necessary for diagnostic purposes in man.