Treatment of parkinsonism with L‐thereo‐3, 4‐dihydroxyphenylserine

Suzuki, Tomokazu; Sakoda, Saburo; Ueji, Masao; Kishimoto, Susumu; Hayashi, Akira; Kondo, Tomoyoshi; Narabayashi, Hirotaro

doi:10.1212/wnl.34.11.1446

Cited by 28 publications

(11 citation statements)

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“…In patients with neurogenic orthostatic hypotension in the setting of PD, treatment with Sinemet™, which contains carbidopa, would be expected to prevent pressor responses to L-DOPS, due to interference with the conversion of L-DOPS to NE (98). Neurogenic orthostatic hypotension in PD has gained attention only relatively recently (18).…”

Section: L-dops 195mentioning

confidence: 99%

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L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Goldstein

2006

Cardiovascular Drug Reviews

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L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

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Section: L-dops 195mentioning

confidence: 99%

“…Neurogenic orthostatic hypotension in PD has gained attention only relatively recently (18). Inadequate consideration of effects of Sinemet™ treatment in this group might help explain variable results of clinical trials of L-DOPS to treat neurogenic orthostatic hypotension overall (6,65,98,108).…”

Section: L-dops 195mentioning

confidence: 99%

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Goldstein

2006

Cardiovascular Drug Reviews

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“…Clinical trials have shown the effectiveness of L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic norepinephrine precursor, on the freezing phenomenon (Narabayashi et al, 1981(Narabayashi et al, , 1987. However, it has been reported that free NE (Suzuki et al, 1984) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (Yamamoto et al, 1986) concentrations in the CSF did not change after administration of L-threo-DOPS.…”

Section: Introductionmentioning

confidence: 99%

The effects of L-threo-3,4-dihydroxyphenylserine on the total norepinephrine and dopamine concentrations in the cerebrospinal fluid and freezing gait in parkinsonian patients

Tohgi

Abe

Takahashi

1993

J Neural Transm Gen Sect

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We studied the effects of L-threo-DOPS (L-DOPS) on the concentrations of total (conjugated and unconjugated) dopamine (DA) and norepinephrine (NE) in the cerebrospinal fluid (CSF) of parkinsonian patients with freezing phenomenon. The NE concentration increased remarkably and dose-dependently after administration of L-DOPS in both L-dopa/carbidopa-pretreated and untreated patients. The DA concentration also increased mildly but significantly in L-dopa/carbidopa-untreated patients. Freezing phenomenon improved in 6 out of 8 patients at Hoehn and Yahr's stage III, and 1 out of 5 patients at stage IV. These results indicate that L-DOPS administration increases the NE concentration dose-dependently, and is effective for freezing of gait of moderate severity.

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“…The ability of DL-DOPS to increase cerebral NE concentration in humans, on the other hand, remains more controversial. Although DOPS has been detected in cerebrospinal fluid Narabayashi et al 1984), no significant changes have been observed in CSF levels of MHPG (Kondo and Narabayashi 1985;Ogawa et al 1985;Yamamoto et al 1985) or NE Sakoda et al 1985) following DOPS administration.…”

Section: Oisials~onmentioning

confidence: 99%

“…Langlais the freezing phenomenon in Parkinsonism (Narabayashi et al 1981(Narabayashi et al , 1984Ogawa et al 1985;Reches et al 1985;Yamamoto et al 1985). The results of chronic clinical trials, as well as detailed acute pharmacokinetic analysis and cardiovascular monitoring in humans ) and cats (Redmond et al 1975), have shown a lack of untoward side effects following DOPS administration.…”

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Memory effect of dl-threo-3,4-dihydroxyphenylserine (DOPS) in human Korsakoff's disease

et al. 1988

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A group of amnesic patients with Korsakoff's disease were treated with a single 1 g dose of DL-threo-3,4-dihydroxyphenylserine (DOPS) and placebo (lactose) in a double-blind crossover study. Three hours following administration, patients were given a battery of psychometric tests to determine the effects of the treatment on memory functions. Administration of DOPS had a significant effect on performance on the Memory Passages test but not on any of the other measures of memory. The effect of DOPS on Memory Passages is similar to the response observed following administration of clonidine in Korsakoff patients. Blood pressure and pulse, measured before and every 2 h after treatment, were unaffected by DOPS.

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Treatment of parkinsonism with L‐thereo‐3, 4‐dihydroxyphenylserine

Cited by 28 publications

References 0 publications

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

The effects of L-threo-3,4-dihydroxyphenylserine on the total norepinephrine and dopamine concentrations in the cerebrospinal fluid and freezing gait in parkinsonian patients

Memory effect of dl-threo-3,4-dihydroxyphenylserine (DOPS) in human Korsakoff's disease

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