Tryptophan 5-HTP 5-HT 5-HT 5-HT SERT 5HT 5HT 5-HT1 5-HT1 B 5-HT2 5-HT2 C Postsynaptic Postsynaptic 5-HT2 5-HT2 A Tryptophan MAO MAO 5-HIAA 5-HT1 5-HT1 A 5-HT1 5-HT1 B 5-HT1 5-HT1 A 5-HT 5-HT 5-HT 5-HT TPH TPH AADC AADC Presynaptic Presynaptic LNAA LNAA
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Tryptophan 5-HTP 5-HT 5-HT SERT 5HT 5-HT1 B 5-HT2 C Postsynaptic 5-HT2 A TryptophanMAO 5-HIAA 5-HT1 A 5-HT1 B 5-HT1 A 5-HT 5-HT TPH AADCPresynapticLNAA.
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Tryptophan
5-HTP
5-HT
5-HT5-HT
SERT
5HT5HT
5-HT15-HT1BB5-HT25-HT2CC
PostsynapticPostsynaptic
5-HT25-HT2AA
Tryptophan
MAOMAO
5-HIAA
5-HT15-HT1AA
5-HT15-HT1BB
5-HT15-HT1AA
5-HT5-HT
5-HT5-HT
TPHTPH
AADCAADC
PresynapticPresynapticLNAALNAA
””Criteria for Assessing Criteria for Assessing Neurotoxicity:Neurotoxicity:
Is 2’-NHIs 2’-NH22-MPTP a-MPTP aSerotonergic Neurotoxin?"Serotonergic Neurotoxin?"
2’-NH2’-NH22-MPTP is Unique Among Ortho--MPTP is Unique Among Ortho-substituted Analogs of MPTPsubstituted Analogs of MPTP
• Decreases in TPH activityDecreases in TPH activity
• Decreases in [Decreases in [33H]5-HT uptakeH]5-HT uptake
• Demonstration of swollen immunoreactive axons and Demonstration of swollen immunoreactive axons and subsequent decrease in fiber densitysubsequent decrease in fiber density
• Decreases in the density of radiolabeled SERTDecreases in the density of radiolabeled SERT
• Decreases in TPH activityDecreases in TPH activity
• Decreases in [Decreases in [33H]5-HT uptakeH]5-HT uptake
• Demonstration of swollen immunoreactive axons and Demonstration of swollen immunoreactive axons and subsequent decrease in fiber densitysubsequent decrease in fiber density
• Decreases in the density of radiolabeled SERTDecreases in the density of radiolabeled SERT