Striatal Dopamine Transporter Modulation After Rotigotine: Results From a Pilot Single-Photon Emission Computed Tomography Study in a Group of Early Stage Parkinson Disease Patients.

Abstract

INTRODUCTION:

Several in vitro data have reported negative interference by dopamine-agonists on the expression of dopamine transporter (DAT), whereas the majority of imaging studies have shown that neither L-dopa nor dopamine-agonists interfere with DAT availability. As yet, there are no in vivo studies on DAT expression after treatment with rotigotine.

METHODS:

We evaluated presynaptic nigrostriatal function in 8 patients with de novo Parkinson disease (age, 59 ± 6.2 years; male/female sex, 5/3) using 123-I- N-ω-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl)nortropane (FP-CIT) single-photon emission computed tomography before and after 3 months of treatment with rotigotine (mean dose, 7.75 ± 1.98 mg). For data analysis, specific (left and right caudate, left and right putamen) to nonspecific (occipital cortex) binding ratios, putamen-to-caudate ratios, and asymmetry indices were calculated.

RESULTS:

After rotigotine, motor symptoms improved in all patients (Unified Parkinson Disease Rating Scale III mean score, 11.88 ± 2.59 vs 7.63 ± 1.92 on therapy; P = 0.0022). Striatal FP-CIT levels showed a significant improvement in every patient at the follow-up scan. Comparisons between before and after treatment in the whole group revealed a significant improvement in FP-CIT uptake in both caudate and putamen (P < 0.001 in each nucleus). Putamen-to-caudate ratio and asymmetry indices did not show any significant difference before and after treatment.

DISCUSSION:

Although the study population was small, we found DAT overexpression after chronic treatment with rotigotine, presumably related to its pharmacological profile. The DAT upregulation by rotigotine in an opposite direction with respect to early Parkinson disease compensatory mechanisms might reduce the risk of dyskinesia, but it could imply less motor benefit because of less stimulation by the dopamine itself on dopaminergic receptors.

• Authors: Carlo Rossi, Dario Genovesi, Paolo Marzullo, Assuero Giorgetti, Elena Filidei, Giovanni Umberto Corsini, Ubaldo Bonuccelli, Roberto Ceravolo
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) 2017 Jan/Feb Vol. 40 Issue 1 Pg. 34-36 ISSN: 1537-162X [Electronic] United States
• PMID: 27941527 (Publication Type: Journal Article)

Chemical References

• Dopamine Agonists
• Dopamine Plasma Membrane Transport Proteins
• Tetrahydronaphthalenes
• Thiophenes
• Tropanes
• 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
• rotigotine

Topics

• Aged
• Cohort Studies
• Corpus Striatum (diagnostic imaging, drug effects)
• Dopamine Agonists (therapeutic use)
• Dopamine Plasma Membrane Transport Proteins (metabolism)
• Female
• Humans
• Male
• Middle Aged
• Parkinson Disease (diagnostic imaging, drug therapy, pathology)
• Pilot Projects
• Prospective Studies
• Tetrahydronaphthalenes (therapeutic use)
• Thiophenes (therapeutic use)
• Tomography, Emission-Computed, Single-Photon
• Treatment Outcome
• Tropanes (pharmacokinetics)