Development of I-123-N-isopropyl-p-iodoamphetamine

The racemic compound, N-isopropyl-p-iodoamphetamine (IMP) was identified and chosen as one of the most promising agents for our further investigation. IMP was synthesized from phenylacetone or p-amino-phenylacetic acid. The starting material for carrier-free I-123-IMP, the bromo analogue of IMP, was synthesized from p-bromo-phenylacetonitrile. The direct exchange reaction of Nal-123 with IMP gave I-123-IMP in greater than 80% radiochemical yield. The tissue distribution of I-125-IMP in rats at 24 hr post injection showed that 1.6, 1.3, 5.0 and 1.1% dose/gm localized in brain, liver, lungs and kidneys, respectively. At 24 hours after I.V. injection, the major metabolite found in the brain, lungs, and liver was p-iodoamphetamine, whereas, besides 30% p-iodoamphetamine and 12% unchanged IMP, p-iodohippuric acid and p-iodobenzoic acid accounted for nearly 40% of the total radioactivity excreted in urine. The LD50 was 82 mg/kg in male mice, 94 mg/kg in female mice, and 46 mg/kg in rats. No signs of CNS stimulation were observed after doses of up to 3 mg/kg in dogs. CNS effects were seen at 10 mg/kg dose. For the subacute study, no significant effect was seen with doses of 1.6 mg/kg/day for 2 weeks in rats. Likewise, no toxic or pharmacological effect was seen with doses of 0.1 mg/kg/day for 2 weeks in dogs. IMP was also shown to be non-mutagenic with Ames Test. The recommended maximum dose of M123 is 1.4 mg. A high dose was seen in thyroid probably due to ionic iodide present in the samples used in these studies. (Namekawa, K.)