STUDIES ON REGIONAL PENETRATION AND ACCUMULATION OF C14 PYRIDINE 2-ALDOXIME METHIODIDE (PAM) IN BRAIN
Abstract
This report includes: THE SYNTHESIS OF PYRIDINE-2-ALDOXIME-C14 METHIODIDE (2-PAM-C14), by Leon Clark and Lloyd J. Roth. 16 May 62. (Grant DA-CML-18-108-61-G-8) Pyridine-2-aldoxime-C-14 methiodide (2-PAM-C-14) was synthesized from 2-bromopyridine and potassium cyanide-C-14. Distribution of the 2-PAMC-14 and its metabolites in the rat was determined 10 min. after a single IV injection. The concentration ratios of unmetabolized PAM in various perfused brain regions relative to the concentration in the plasma indicated that it had not only entered the extracellular space, but penetrated beyond, disproving the previously held opinion that it does not enter the C.N.S. Comparison of whole blood and plasma levels also demonstrated that it had penetrated erythrocytes. Pretreatment with the cholinesterase inhibitor dipterex enhanced the penetration of PAM into the brain. Hypercapnea produced by CO(2) pretreatment also increased the concentration in various regions of the brain. Chromatographic resolution of the urine revealed 11 distinct bands with the major portion of the activity residing in the unmetabolized 2-PAM-C-14 band. N-methyl and oxime labeled 2-PAM yielded similar results.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1962
- Accession Number
- AD0282747
Entities
People
- Lloyd J. Roth
Organizations
- University of Chicago