benzofurans and Supranuclear-Palsy--Progressive

We have tested, in a prospective randomized, double-blind, placebo-controlled, crossover, 12-week study, the effects of 2 mg efaroxan, a potent alpha-2 antagonist, given three times per day to 14 patients with progressive supranuclear palsy. Efaroxan did not induce any significant change on any motor assessment criteria. The present data do not confirm the assumption that the blockade of alpha-2 receptors might be a useful pharmacologic strategy to improve patients with progressive supranuclear palsy.

Topics: Adrenergic alpha-Antagonists; Adult; Aged; Benzofurans; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Imidazoles; Male; Middle Aged; Neurologic Examination; Prospective Studies; Supranuclear Palsy, Progressive; Treatment Outcome

[. To test the hypothesis that the MAO-B inhibitor, rasagiline reduces [. Six individuals (4: PSP; 2: cognitively unimpaired, CU) underwent [. The post-rasagiline regional SUV was reduced on average by 69-89% in PSP, and 53-81% in CU. The distributions of post-rasagiline [. Similar to AD, the interpretation of [

Topics: Aged; Aged, 80 and over; Aminopyridines; Benzofurans; Female; Humans; Hydrocarbons, Fluorinated; Indans; Male; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurofibrillary Tangles; Positron-Emission Tomography; Quinolines; Radiopharmaceuticals; Supranuclear Palsy, Progressive; tau Proteins

To investigate the clinical applicability and validity of [123I] iodobenzofuran (IBF) single-photon emission computed tomography (SPECT), the authors analyzed the changes in striatal dopamine D2 receptor binding among 7 patients with Parkinson's disease (PD), 6 patients with progressive supranuclear palsy (PSP) (Hoehn and Yahr stage II to IV), and 8 normal controls.. SPECT data were acquired every 1 minute for 60 minutes postinjection of 167 MBq [123I] IBF. The binding potential (BP) of the striatum was evaluated by 2 methods: region-of-interest (ROI) analysis by the nonlinear least squares method using blood sampling and time-series brain radioactivities in normal controls and a voxel-by-voxel method based on a region model that provided parametric images of BP without blood sampling.. Statistical parametric mapping indicated that BP in the striatum of PSP patients was significantly lower than that of PD patients and normal controls (P < .005, uncorrected), and there was no significant difference between PD patients and normal controls, even in patients with PD at an advanced stage. Data derived from the ROI method and a simplified reference region model showed good correlations in normal controls, indicating the validity of the latter model.. The results predict that [123I] IBF SPECT, especially voxel-by-voxel BP parametric imaging, can discriminate among extrapyramidal diseases such as PD and PSP and may be applicable for clinical use.

Topics: Adult; Aged; Benzofurans; Case-Control Studies; Corpus Striatum; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Least-Squares Analysis; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Receptors, Dopamine D2; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon

Iodine-123-IBF is a dopaminergic antagonist suitable for SPECT imaging of D2 receptors. Initial animal studies demonstrated that its affinity for D2 receptors is approximately four times that of the commonly used SPECT D2 ligand [123I]IBZM. In this study we investigated whether this higher affinity would lead to an improved accuracy in differentiating between various extrapyramidal diseases.. SPECT imaging was performed in 17 patients with idiopathic Parkinson's syndrome (IPS); 4 patients with progressive supranuclear palsy (PSP), 2 patients with multiple system atrophy (MSA) and 7 age-matched control subjects. SPECT imaging was performed 5, 60, 120 and 180 min following intravenous bolus injection of 150-250 MBq of [123I]IBF. The ratio of ligand uptake in the basal ganglia and frontal cortex was determined as a measure of receptor status.. In PSP and MSA patients, the basal ganglia-to-frontal cortex ratio reached a plateau at 2 hr; in the control subjects and the IPS patients the ratio was steadily increasing. At 3 hr the basal ganglia-to-frontal cortex ratio was 2.66 +/- 0.29 (control subjects), 3.01 +/- 0.41 (IPS), 2.09 +/- 0.22 (PSP) and 2.10 (MSA). In the IPS patients with predominantly one-sided symptoms, the striatum contralateral to symptoms showed a tendency towards relatively increased ligand uptake. Despite the higher affinity of IBF for the D2 receptor compared to IBZM, the separation of individual PSP and MSA patients from the control subjects was not as clear cut as reported for IBZM due to a relatively high variation in the control subjects. We hypothesize that the latter is due to imaging in nonequilibrium conditions.. The data suggest that IBF-SPECT can help in discriminating extrapyramidal disease. The accuracy might be improved by an administration protocol that allows imaging in "true equilibrium" conditions, such as a bolus injection followed by a constant infusion.

Topics: Aged; Aged, 80 and over; Basal Ganglia; Basal Ganglia Diseases; Benzofurans; Brain; Diagnosis, Differential; Female; Frontal Lobe; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Pyrrolidines; Receptors, Dopamine D2; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon