The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson's disease

被引:3
作者
Marano, Massimo [1 ,2 ]
Pilotto, Andrea [3 ,4 ,5 ,6 ]
Padovani, Alessandro [3 ,4 ,5 ,6 ]
Gupta, Deepak [7 ]
Vivacqua, Giorgio [8 ]
Magliozzi, Alessandro [1 ,2 ]
Di Lazzaro, Vincenzo [1 ,2 ]
Carta, Manolo [9 ]
Meloni, Mario [10 ]
机构
[1] Univ Campus Biomed Roma, Dept Med, Neurol Neurobiol & Psychiat Unit, Via Alvaro Portillo 200, I-00128 Rome, Italy
[2] Fdn Policlin Univ Campus Biomed, Viale Alvaro Portillo 200, I-00128 Rome, Italy
[3] Univ Brescia, Dept Clin & Expt Sci, Neurol Unit, Brescia, Italy
[4] Univ Brescia, Lab Digital Neurol & Biosensors, Brescia, Italy
[5] ASST Spedali Civili Brescia Hosp, Dept Continu Care & Frailty, Neurol Unit, Brescia, Italy
[6] Univ Brescia, Brain Hlth Ctr, Brescia, Italy
[7] Univ Vermont, Larner Coll Med, Dept Neurol Sci, Burlington, VT USA
[8] Univ Campus Biomed Roma, Lab Microscop & Ultrastruct Anat, Via Alvaro Portillo 21, I-00128 Rome, Italy
[9] Univ Cagliari, Dept Biomed Sci, Cagliari, CA, Italy
[10] Azienda Ospedaliera Univ Cagliari, Neurol Unit, Cagliari, Italy
关键词
Levodopa-induced dyskinesias; Locus coeruleus; Noradrenaline; Serotonin; Motor fluctuations; Depression; DOPA-INDUCED DYSKINESIA; NORADRENERGIC DENERVATION; ANIMAL-MODELS; TRANSPORTER; NEURONS;
D O I
10.1007/s00415-024-12400-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Parkinson's disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology. Methods We performed a longitudinal analysis on the PPMI cohort including drug-na & iuml;ve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up. Results LID prevalence (according to MDS UPDRS score 4.1 >= 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 +/- 1.07 vs 2.6 +/- 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001). Discussion This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association.
引用
收藏
页码:3711 / 3720
页数:10
相关论文
共 30 条
[1]   Reuptake of L-DOPA-Derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter [J].
Arai, Akira ;
Tomiyama, Masahiko ;
Kannari, Kazuya ;
Kimura, Tamaki ;
Suzuki, Chieko ;
Watanabe, Mitsunori ;
Kawarabayashi, Takeshi ;
Shen, Huo ;
Shoji, Mikio .
SYNAPSE, 2008, 62 (08) :632-635
[2]   Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats [J].
Barnum, Christopher J. ;
Bhide, Nirmal ;
Lindenbach, David ;
Surrena, Margaret A. ;
Goldenberg, Adam A. ;
Tignor, Stefanie ;
Klioueva, Anna ;
Walters, Hannah ;
Bishop, Christopher .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2012, 100 (03) :607-615
[3]   Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia [J].
Bezard, Erwan ;
Tronci, Elisabetta ;
Pioli, Elsa Y. ;
Li, Qin ;
Porras, Gregory ;
Bjorklund, Anders ;
Carta, Manolo .
MOVEMENT DISORDERS, 2013, 28 (08) :1088-1096
[4]   Parkinson's disease [J].
Bloem, Bastiaan R. ;
Okun, Michael S. ;
Klein, Christine .
LANCET, 2021, 397 (10291) :2284-2303
[5]   Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in Parkinsonian rats [J].
Carta, Manolo ;
Carlsson, Thomas ;
Kirik, Deniz ;
Bjorklund, Anders .
BRAIN, 2007, 130 :1819-1833
[6]   The serotonergic system in L-DOPA-induced dyskinesia: pre-clinical evidence and clinical perspective [J].
Carta, Manolo ;
Bjorklund, Anders .
JOURNAL OF NEURAL TRANSMISSION, 2018, 125 (08) :1195-1202
[7]   Post-versus presynaptic plasticity in L-DOPA-induced dyskinesia [J].
Cenci, M. Angela ;
Lundblad, Martin .
JOURNAL OF NEUROCHEMISTRY, 2006, 99 (02) :381-392
[8]  
Chase Thomas N., 1998, Neurology, V50, pS17
[9]   Norepinephrine Transporter Inhibition with Desipramine Exacerbates L-DOPA-Induced Dyskinesia: Role for Synaptic Dopamine Regulation in Denervated Nigrostriatal Terminals [J].
Chotibut, Tanya ;
Fields, Victoria ;
Salvatore, Michael F. .
MOLECULAR PHARMACOLOGY, 2014, 86 (06) :675-685
[10]   Dopamine Transporter Loss in 6-OHDA Parkinson's Model Is Unmet by Parallel Reduction in Dopamine Uptake [J].
Chotibut, Tanya ;
Apple, Deana M. ;
Jefferis, Rebecca ;
Salvatore, Michael F. .
PLOS ONE, 2012, 7 (12)