Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Diagnostic and Pathophysiological Impact of FP-CIT SPECT in Parkinson s Disease

Author(s): Jorg Spiegel.

Abstract:

Idiopathic Parkinsons disease (PD) is characterized by a Lewy body-degeneration of presynaptic nigrostriatal dopaminergic neurons. This degeneration can be visualized by nuclear medicine methods, primarily by FP-CIT SPECT: Fluoropropyl-Carbomethoxy-Iodophenyl-Tropan (FP-CIT), marked by radioactive 123iodine, binds to dopamine reuptake transporters at the presynaptic membrane of the nigral dopaminergic neuron. Due to its fast and highly affine binding (Ki = 3.1 nM) to dopamine transporters, FP-CIT SPECT is the most favored nuclear medicine method to support the diagnosis of PD. FP-CIT SPECT shows a high sensitivity concerning PD (95%-100%), a high specificity against essential tremor (100%), but a rather low specificity against atypical parkinsonian syndromes. FP-CIT SPECT reflects the nigrostriatal dopaminergic function in PD, since FP-CIT SPECT correlates significantly with the motor part of the UPDRS (Unified Parkinson´s disease rating scale) score. Recently we correlated the nigrostriatal FP-CIT uptake with parkinsonian cardinal symptoms hypokinesia, rigidity, resting tremor and postural tremor: nigrostriatal FP-CIT uptake correlated significantly inversely with the extent of hypokinesia and rigidity, but there was no correlation between FP-CIT uptake versus resting or postural tremor. These findings correspond to clinical observations that hypokinesia and rigidity – rather than resting or postural tremor - respond well to dopaminergic drugs. Accordingly histopathological studies disclosed a Lewy bodydegeneration not only of dopaminergic neurons but also of serotoninergic and cholinergic nuclear grays. Nuclear medicine examinations of further cerebral transmitter systems - primarily of the serotoninergic and the cholinergic system – seem to be necessary to understand the pathophysiology of resting and postural tremor in PD.

Keywords: FP-CIT SPECT, Parkinson's disease, atypical parkinsonian syndromes

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Article Details

VOLUME: 7
ISSUE: 3
Year: 2007
Page: [173 - 176]
Pages: 4
DOI: 10.2174/187152407781669134
Price: $58