Session 5: Neuroscience I Receptors, Proteins-Chemistry and Pharmacology

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 596 KB
• Volume: 46
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.754

✦ Synopsis

Monoamine oxidase (MAO) is a key regulatory and protective enzyme because its substrates include many physiologically active amines including neurotransmitters, drugs and dietary amines. It occurs in two different subtypes, MAO A and MAO B which are different gene products and have different substrate and inhibitor specificities (reviewed in Shih et al, 1999). The relative ratios of MAO A and B are both organ and species dependent making it difficult to use animals as a model for humans (Inoue et al., 1999). The purpose of this study is to compare the irreversible MAO A and B radiotracers [ 11 C]clorgyline (CLG) and [ 11 C]L-deprenyl (DEP) and their deuterium substituted counterparts (CLG-D and DEP-D) as tracers for measuring MAO A and B in peripheral organs with respect to isotope effect, binding rate, sensitivity to blood flow, and differences in organ distribution. Deuterium substitution was in the methylene carbon of the propargyl group which is the bond known to be cleaved by MAO oxidation.

CLG

CLG-D DEP DEP-D Methods: CLG and CLG-D were imaged for 60 min with PET in 12 healthy human subjects and the results compared with 9 subjects imaged previously with DEP and DEP-D (Fowler et al., 2002). Normalized uptake was measured from the average uptake at plateau (20-60 min) divided by the plasma integral of tracer from injection to end of study (incorporation quotient, IQ). A 3-O N Cl