Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice

Serrano, Alba; Menéndez, Jaime; Casarejos, Marı́a José; Solano, Rosa M.; Gallego, Eva; Sánchez, Marina P.; Mena, María A.; Yébenes, Justo Garcı́a de

doi:10.1016/j.neuropharm.2005.03.003

Cited by 29 publications

(23 citation statements)

References 28 publications

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“…GSH levels decrease with aging in vivo (Rodriguez-Navarro et al, 2007). Young PK-KO mice had high levels of GSH in striatum (Itier et al, 2003;Serrano et al, 2005), but they decreased with age. Reduced GSH, as happens in striatum or in aged glial cultures, may become lethal for nigrostriatal neurons because these cells have a high dopamine-related production of free radicals, and they are protected by a smaller proportion of astrocytes than neurons in other brain areas (Damier et al, 1993).…”

Section: Discussionmentioning

confidence: 94%

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Solano¹,

Casarejos²,

et al. 2008

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Parkin mutations in humans produce parkinsonism whose pathogenesis is related to impaired protein degradation, increased free radicals, and abnormal neurotransmitter release. The role of glia in parkin deficiency is little known. We cultured midbrain glia from wild-type (WT) and parkin knock-out (PK-KO) mice. After 18 -20 d in vitro, PK-KO glial cultures had less astrocytes, more microglia, reduced proliferation, and increased proapoptotic protein expression.PK-KO glia had greater levels of intracellular glutathione (GSH), increased mRNA expression of the GSH-synthesizing enzyme ␥-glutamylcysteine synthetase, and greater glutathione S-transferase and lower glutathione peroxidase activities than WT. The reverse happened in glia cultured in serum-free defined medium (EF12) or in old cultures. PK-KO glia was more susceptible than WT to transference to EF12 or neurotoxins (1-methyl-4-phenylpyridinium, blockers of GSH synthesis or catalase, inhibitors of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3 kinases), aging of the culture, or combination of these insults. PK-KO glia was less susceptible than WT to Fe 2ϩ plus H 2 O 2 and less responsive to protection by deferoxamine. Old WT glia increased the expression of heat shock protein 70, but PK-KO did not. Glia conditioned medium (GCM) from PK-KO was less neuroprotective and had lower levels of GSH than WT. GCM from WT increased the levels of dopamine markers in midbrain neuronal cultures transferred to EF12 more efficiently than GCM from PK-KO, and the difference was corrected by supplementation with GSH. PK-KO-GCM was a less powerful suppressor of apoptosis and microglia in neuronal cultures. Our data prove that abnormal glial function is critical in parkin mutations, and its role increases with aging.

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Section: Discussionmentioning

confidence: 94%

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Solano¹,

Casarejos²,

et al. 2008

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“…Other L-type calcium channel blockers such as cinnarizin can also induce parkinsonism [15]. The mechanism is not fully understood, but both an antidopaminergic effect and direct neurotoxicity have been suggested [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism is not fully understood, but both an antidopaminergic effect and direct neurotoxicity have been suggested [14,15]. Gait analysis conducted with pregabalin (left), 11 days after reinstitution of 75 mg bid, and without pregabalin (right), 7 days after its probative withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Pregabalin: a treatment option for dystonia?

Karosin¹,

Kofler²,

Mayr³

et al. 2011

Neurol Sci

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To date, no studies are available on the effect of pregabalin in dystonia. A patient with subarachnoidal and cerebral hemorrhage was treated with pregabalin for neuropathic pain. Upon withdrawal of the medication she experienced spontaneous and painful supination in the right foot and internal hip rotation when standing up. When pregabalin was reinstituted, these dystonic symptoms subsided, but reappeared when the medication was again discontinued. One possible explanation for these symptoms could be neuronal hyperactivity within still-functioning pathways in connection with the motor cortex. Preponderance of activity in potentially compensatory structures could be suppressed by pregabalin: therefore, its potential benefit in subacute secondary dystonia in cases with orbital brain involvement is suggested.

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“…Например, было отмечено, что, кроме блокады D2-рецепторов в полосатом теле, на фоне приема циннаризина может снижаться уровень пресинаптического дофамина и нарушаться работа везикулярного транспортера дофа-мина [39]. Развитию лекарственно-спровоцированной БП наиболее подвержены пациенты с положительным семейным анамнезом по БП или генетической пред-расположенностью к БП [40]. Риск развития лекарствен-ного паркинсонизма на фоне циннаризина прямо пропорцио нален длительности приема [41].…”

Section: проблема лекарственного паркинсонизма при применении циннариunclassified

Possibilities to Use a Fixed Combination of Piracetam and Cinnarizine in Neurological Practice

Titova¹

2017

Med. sov.

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ПРАКТИКА ВВЕДЕНИЕВ последние годы в неврологии, как и во многих других областях медицины, все бо льшую популярность завоевы-вают комбинированные препараты, содержащие два активных компонента. В первую очередь это связано с открытием новых механизмов, лежащих в основе невро-логических расстройств. Вовлечение нескольких звеньев в патогенез большинства заболеваний нервной системы на практике выражается в необходимости использования препаратов с разными точками приложения, с разными механизмами действия. Как следствие одновременного назначения нескольких препаратов, невролог нередко сталкивается с проблемой низкой приверженности к лечению. Достижением современной фармакотерапии является разработка и внедрение в клиническую практи-ку препаратов с комбинированным составом, т. е. оптими-зация лечебного процесса. Такие лекарственные формы включают в себя активные компоненты со сбалансиро-ванным разносторонним влиянием на патологические процессы заболевания, с одной стороны, и в адекватных дозах, не приводящих к усилению побочных эффектов или развитию непредсказуемых фармакологических вза-имодействий, с другой стороны. Примером такого сочета-

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Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice

Cited by 29 publications

References 28 publications

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Pregabalin: a treatment option for dystonia?

Possibilities to Use a Fixed Combination of Piracetam and Cinnarizine in Neurological Practice

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