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N-Isopropyl-[¹²³I] p-Iodoamphetamine: Single-Pass Brain Uptake and Washout; Binding to Brain Synaptosomes; and Localization in Dog and Monkey Brain

Medi-Physics, Inc., Emeryville, California
Roche Laboratories, Nutley, New Jersey
Brentwood VA Hospital, Los Angeles
University of California at San Francisco, San Francisco, California

Correspondence: For reprints contact: H.S. Winchell, MD, Medi-Physics, Inc., 5855 Christie Ave., Emeryville, CA 94608.

ABSTRACT

The kinetics of N-Isopropyl-p-[¹²³I]iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. Serial BUI correspond to a first-pass extraction efficiency of 100% and a washout half-time of 318 sec. The S-(+)- isomer inhibited norepinephrine uptake in synaptosomes as strongly as D-amphetamine, but was more potent in inhibiting synaptosomal uptake of serotonin. Both isomers were comparable to D-amphetamine in causing release of serotonin from synaptosomes, but the S-(+)- isomer promoted release of dopamine, whereas D-amphetamine did not. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours. The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism.

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