Observations on the Efficacy of L-Dopa in Progressive Supranuclear Palsy

Klawans, H. L.; Ringel, Steven P.

doi:10.1159/000114065

Cited by 41 publications

(18 citation statements)

References 6 publications

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“…Whereas patients with PSP occasionally respond,20 29 the improvement is typically short lived and insufficient to alter major disability. 29 Similarly, two of our cases responded to levodopa, but with no more than moderate and short lived benefit. Thus lack of an impressive sustained improvement with levodopa is an important diagnostic clue.…”

Section: Discussionsupporting

confidence: 50%

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

Collins

Ahlskog

Parisi

et al. 1995

Journal of Neurology, Neurosurgery & Psychiatry

197

105

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Section: Discussionsupporting

confidence: 50%

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

Collins

Ahlskog

Parisi

et al. 1995

Journal of Neurology, Neurosurgery & Psychiatry

197

105

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“…Cholinergic drugs, for example, do alleviate psychoses while aggravating parkinsonism and have acted on the cyclase concordantly (7,8). When given with L-dopa, anticholinergics are somewhat more potent as antiparkinsonism agents (22,23).…”

Section: Resultsmentioning

confidence: 99%

“…To this end we used adenylate cyclase from mouse caudate to screen agents that can affect the symptoms of Parkinson's disease. These included drugs that stimulate the dopaminergic system in man or animals and inactive metabolites and precursors thereof and compounds that activate or inhibit the cholinergic system, which counterbalances the dopaminergic one in the brain (7,8).MATERIALS AND METHODS Animals. These were 5-to 6-week-old male Swiss albino mice, weighing 23-27 g, maintained on Purina Chow and water ad lib., and kept in an air-conditioned room on a 12-hr lightto-darkness cycle.…”

mentioning

confidence: 99%

Opposing effects of dopaminergic to cholinergic compounds on a cerebral dopamine-activated adenylate cyclase.

Tang¹,

Cotzias²

1977

Proc. Natl. Acad. Sci. U.S.A.

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We have studied these possibilities in the hope of advancing the treatments of Parkinson's disease and of psychosis. To this end we used adenylate cyclase from mouse caudate to screen agents that can affect the symptoms of Parkinson's disease. These included drugs that stimulate the dopaminergic system in man or animals and inactive metabolites and precursors thereof and compounds that activate or inhibit the cholinergic system, which counterbalances the dopaminergic one in the brain (7,8).MATERIALS AND METHODS Animals. These were 5-to 6-week-old male Swiss albino mice, weighing 23-27 g, maintained on Purina Chow and water ad lib., and kept in an air-conditioned room on a 12-hr lightto-darkness cycle. The experiments were started in midday by decapitating the animals in a cold room. The brains were removed within 30 sec and placed on a cold watch glass. The lateral ventricles were entered by removing their roofs. The exposed heads of the caudates were scooped out with forceps.Determination of Dopamine-Stimulated Adenylate Cyclase Activity. The methods are essentially those developed in Greengard's laboratory (9). All fragments of both caudates (about 30 mg) were placed in Krebs-Ringer bicarbonate solution, pH 7.4, which had been gassed for 2 min with 5% CO2/ 95% 02. They were homogenized in 0.5 ml of 50 mM Trismaleate buffer, pH 7.4, containing 12.5 mM theophylline, 0.25 mM ethylene glycol-bis(Q-aminoethyl ether)-NN'-tetraacetic acid, and 2.5 mM MgSO4. Aliquots (0.4 ml) of the homogenates were placed in 5-ml Pyrex tubes that had previously been equilibrated to 30°in an orbital water bath. The control tubes received 50 gl of H20. The experimental tubes received different additives in different series of experiments, the concentrations of which are given below. In one series, 50 ,ul containing either dopamine or a dopaminergic substance was added. In another series, the tubesi received 25 ,ul containing one of the above substances plus 25 jul containing-an inhibitor, a metabolite, or a precursor thereof. In another series, the precursors and metabolites were tested in various concentrations for activation of the cyclase. In still another series, the metabolites were screened for inhibition of the dopamine-dependent activation. Finally, some cholinergic and anticholinergic agents were screened for activation or inhibition of the cyclase.The reaction was started by adding 50 jul of a 0.5 mM solution of ATP with mixing and then incubating in a 30°orbital water bath. After 2.5 min, the reaction was terminated by immersion of the tubes into a boiling water bath for 2 min. The homogenates were centrifuged at 1500 X g for 5 min. The supernatant solutions were quick-frozen until analyzed for adenosine 3': 5'-cyclic monophosphate (cyclic AMP) according to Gilman (10).The results of the cyclic AMP determinations were used as follows. We first computed the mean ±SEM of both nonstimulated and stimulated samples. From these we calculated the net dopamine-stimulated cyclic AMP produced by subtracting the mean nonstimulated acti...

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“…However, without placebo control it is difficult to ascertain whether these are true benefits [Class IV] [57–59]. …”

Section: Treatmentmentioning

confidence: 99%

Treatment of Frontotemporal Dementia

Tsai

Boxer

2014

Curr Treat Options Neurol

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Opinion statement Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative diseases with heterogeneous clinical presentations and two predominant types of underlying neuropathology. FTD typically comprises three distinct clinical syndromes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), and nonfluent variant primary progressive aphasia (nfvPPA). FTD also frequently overlaps both clinically and neuropathologically with three other neurodegenerative syndromes: corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS). Each syndrome can be associated with one or more underlying neuropathological diagnoses and are referred to as frontotemporal lobar degeneration (FTLD). Although the various FTD syndromes can substantially differ in terms of clinical symptoms and underlying pathology, the symptoms can be broadly categorized into behavioral, cognitive and motor domains. Currently there are no Food and Drug Administration (FDA) approved therapies for the above syndromes except riluzole for ALS. FTD treatment strategies generally rely on off-label use of medications for symptomatic management, and most therapies lack quality evidence from randomized, placebo-controlled clinical trials. For behavioral symptoms, selective serotonin reuptake inhibitors may be effective, while case reports hint at possible efficacy with antipsychotics or antiepileptics, but use of these latter agents is limited due to concerns regarding side effects. There are no effective therapies for cognitive complaints in FTD, which frequently involve executive function, memory, and language. Motor difficulties associated with FTD may present with parkinsonian symptoms or motor neuron disease, for which riluzole is indicated as therapy. Compared to idiopathic Parkinson’s disease, FTD-related atypical parkinsonism is generally not responsive to dopamine replacement therapies, but a small percentage of patients may experience improvement with a trial of carbidopa-levodopa. Physical and occupational therapy remain an important corner stone of motor symptom management in FTD. Speech therapy may also help patients manage symptoms associated with aphasia, apraxia, and dysarthria. Recent advances in the understanding of FTLD pathophysiology and genetics have led to development of potentially disease-modifying therapies as well as symptomatic therapies aimed at ameliorating social and behavioral deficits.

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Observations on the Efficacy of L-Dopa in Progressive Supranuclear Palsy

Cited by 41 publications

References 6 publications

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

Opposing effects of dopaminergic to cholinergic compounds on a cerebral dopamine-activated adenylate cyclase.

Treatment of Frontotemporal Dementia

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