L-threo-3,4-dihydroxyphenylserine treatment for akinesia and freezing of Parkinsonism.

Narabayashi, Hirotaro; Kondo, Tomoyoshi; Hayashi, Akira; Suzuki, Tomokazu; Nagatsu, Toshiharu

doi:10.2183/pjab.57.351

Cited by 106 publications

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“…Initial experience with L -DOPS treament which was initiated for the improvement of gait apraxia was promising (Narabayashi et al , 1984(Narabayashi et al and 1986Kondo, 1984;Ogawa et al 1984;Suzuki et al 1984a). In addition, L -DOPS was found to be effective for disease conditions other than parkinsonism and for symptoms other than gait apraxia, such as: juvenile form of parkinsonism ; familial amyloid polyneuropathy (Suzuki et al 1980(Suzuki et al , 1981(Suzuki et al and 1982 ; pure akinesia (Itou ji et al 1984;Yamamoto and Ujike, 1985;Narabayashi et al 1986) ; Shy-Drager's syndrome (Sakoda et al 1985) and neoplasm in the caudate head (Suzuki et al 1984b). Symptoms which responded to L -DOPS include ; gait apraxia ; freezing of speech and writing; depressive state; orthostatic hypertension (Suzuki et al 1981;Birkmayer et al 1983;Sakoda et al 1985) ; up and down phenomenon; L -DOPA induced apraxia and other symptoms of parkinsonism (Kondo, 1984).…”

Section: Resultsmentioning

confidence: 99%

“…Based on these findings, new agents to counteract each deficiency are now being introduced Narabayashi, 1985). L -threo -3, 4 -dihyd roxyphenylserine (L -DOPS) is a precursor of noradrenaline (Corrodi and Fuxe, 1967;Creveling et al 1968;Suzuki et al 1980Suzuki et al , 1982Suzuki et al , 1984Suzuki et al and 1985Edwards and Rizk, 1981;Edwards and Sedlock, 1982;Tanaka and Nishino, 1985). Based on the possible link between noradrenaline deficient state in the central nervous system (CNS) and akinetic symptoms, L -DOPE can be expected to counteract particularly gait related akinesia such as gait apraxia, festination and retropulsion, and possibly other forms of akinesia, all of which are most often noted in patients who had long been on L-DOPA treatment and extremely difficult to control because they are usually ref ractile to L -DOPA treatment (Narabayashi and Nakamura, 1981).…”

Section: Introductionmentioning

confidence: 99%

“…Based on the possible link between noradrenaline deficient state in the central nervous system (CNS) and akinetic symptoms, L -DOPE can be expected to counteract particularly gait related akinesia such as gait apraxia, festination and retropulsion, and possibly other forms of akinesia, all of which are most often noted in patients who had long been on L-DOPA treatment and extremely difficult to control because they are usually ref ractile to L -DOPA treatment (Narabayashi and Nakamura, 1981). Initial reports on clinical trials of L-DOPS for gait related akinesia seem to be promising (Narabayashi et al , 1984(Narabayashi et al and 1986Kondo, 1984;Ogawa et al 1984;Suzuki et al 1984a).…”

Section: Introductionmentioning

confidence: 99%

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L-threo-3,4-dihydroxyphenylserine treatment for gait apraxia in parkinsonian patients.

1989

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Summary : L -threo -3, 4 -dihydroxyphenylserine (L -DOPS) was administered to six parkinisonian patients for the treatment of gait related akinesia which was refractile to L-DOPA treatment.One responded with marked improvement and one with only mild improvement.Although number of patients who respond markedly to this noradrenaline precursor, L-DOPS, is limited, L-DOPS was felt to be the most effective treatment modality for L-DOPA ref ractilegait related akinesia and L-DOPA related orthostatic hypotension.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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L-threo-3,4-dihydroxyphenylserine treatment for gait apraxia in parkinsonian patients.

1989

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“…(6) reported that L threo-DOPS was effective in treating some symptoms of parkinsonism such as akinesia and freezing. Since degeneration of the noradrenaline-containing neurons in the LC concomitantly with degeneration of dopa minergic neurons in the substantia nigra was observed in patients with parkinsonism (7,8), the effects of L-threo-DOPS are considered to be due to supplemental noradrenaline in the brain.…”

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confidence: 99%

Inhibitory Effects of L-Threo-DOPS, an L-Noradrenaline Precursor, on Locus Coeruleus-Originating Neurons in the Caudate Nucleus

Hirose

Sasa

Ohno

et al. 1988

Japanese Journal of Pharmacology

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Abstract-Electrophysiological studies using reserpine-treated cats were carried out to elucidate the effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the noradrenergic pathway from the locus coeruleus (LC) to the caudate nucleus (CN) neurons, which were activated by iontophoretically applied bromocriptine, a dopamine D-2 receptor agonist.In the CN neurons, glutamate-induced firing was inhibited by iontophoretic application of noradrenaline, but not by repetitive stimu lation of the LC or iontophoretically applied L-threo-DOPS. After intraventricular administration of L-threo-DOPS, however, LC stimulation inhibited the glutamate induced firing. These results suggest that L-noradrenaline that was produced from the conversion of L-threo-DOPS inhibited the CN neurons which possess dopamine D-2 receptors.It is well-documented that L-threo-3,4 dihydroxyphenylserine (L-threo-DOPS) is directly converted into L-noradrenaline by L aromatic amino acid decarboxylase in the brain and kidney (1, 2). Systemic adminis tration of L-threo-DOPS to experimental animals, in which monoamines such as noradrenaline were depleted by reserpine or tetrabenazine, is known to increase the noradrenaline level in the brain (3, 4). Our previous studies have also demonstrated that noradrenaline formed from L-threo-DOPS in the locus coeruleus (LC) neurons inhibits the transmission of the spinal trigeminal nucleus neurons (5).Narabayashi et a!. (6) reported that L threo-DOPS was effective in treating some symptoms of parkinsonism such as akinesia and freezing. Since degeneration of the noradrenaline-containing neurons in the LC concomitantly with degeneration of dopa minergic neurons in the substantia nigra was observed in patients with parkinsonism (7, 8), the effects of L-threo-DOPS are considered to be due to supplemental noradrenaline in the brain. Previously, we reported that about one third of the caudate nucleus (CN) neurons activated by stimulation of the pars compacta of the substantia nigra were inhibited by noradrenaline derived from the LC (9). In the CN neurons, the spike elicited by nigral stimulation appears to be induced by dopa mine, which acts on postsynaptic dopamine D-2 receptors, since the spike was blocked by iontophoretically applied domperidone, a dopamine D-2 antagoist, and firing of the neu rons was increased by iontophoretic applica tion of D-2 agonists such as bromocriptine and quinpirole (10-13). Thus, we preformed an electrophysiological study to examine whether or not noradrenaline converted from L-threo-DOPS affects the CN neurons ac tivated by a dopamine D-2 agonist. Materials and MethodsFourteen adult cats weighing 2.6-4.2 kg were given 1 mg/kg, i.m., of reserpine (Daiichi Seiyaku) 24 hr before the experiments. Surgical procedures such as cannulation into the trachea and femoral vein were carried out under ether anesthesia. The head of the animal was fixed in a stereotaxic instrument. After the operation, the ether anesthesia was re placed with a-chloralose (30 mg/kg, i.v.),

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“…It has also been reported that L-DOPS produced a positive chronotropic effect in rat atrial preparations (5) as well as an inotropic effect in open-chest rats (6), a slow onset and long-lasting hypertensive effect in rats (7) and a diuretic effect in rats and mice (8). In clinical studies, DL or L DOPS has recently been reported to improve postual hypotension and dizziness in par kinsonian patients (9), and the patients with familial amyloid polyneuropathy (10) or Shy Drager syndrome (11), and also to show beneficial effect on akinesia or freezing phenomenon in advanced parkinsonian patients (12). In the present study, the effect of L-DOPS on the cerebral blood flow (CBF) was studied in rats in comparison with that of NE.…”

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confidence: 99%

Effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS), an immediate precursor of norepinephrine, on the cerebral blood flow in rats.

Sato¹,

Irie²,

Katsube³

1987

Jpn.J.Pharmacol

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Abstract-L-threo-3,4-Dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) precursor, 3 mg/kg, i.v., increased the cerebral blood flow (CBF) in both the striatum and hippocampus as well as the mean arterial blood pressure (MABP) in urethane-anesthetized rats, as NE infusion did. The L-DOPS induced increase in CBF was inhibited by benserazide (3 mg/kg/hour), a peripheral aromatic L-amino acid decarboxylase inhibitor, and propranolol (3 mg/kg, i.p.), a 19-adrenoceptor blocker as well. These results suggest that the effects of L-DOPS may be at tributed to the action of NE formed from L-DOPS, and the action may be mediated by stimulation of i9-adrenoceptor.A synthetic amino acid, L-threo-3,4 dihydroxyphenylserine (L-DOPS) has been known to be decarboxylated by aromatic L amino acid decarboxylase to yield norepine phrine (NE) in vitro (1) and in vivo (2-4). It has also been reported that L-DOPS produced a positive chronotropic effect in rat atrial preparations (5) as well as an inotropic effect in open-chest rats (6), a slow onset and long-lasting hypertensive effect in rats (7) and a diuretic effect in rats and mice (8). In clinical studies, DL or L DOPS has recently been reported to improve postual hypotension and dizziness in par kinsonian patients (9), and the patients with familial amyloid polyneuropathy (10) or Shy Drager syndrome (11), and also to show beneficial effect on akinesia or freezing phenomenon in advanced parkinsonian patients (12). In the present study, the effect of L-DOPS on the cerebral blood flow (CBF) was studied in rats in comparison with that of NE.The experiments were carried out in male Sprague-Dawley rats weighing between 240 and 310 g. The animals were anesthetized with urethane (1.25 g/kg, i.p.). Polyethylene catheters were inserted into the femoral artery and vein for continuous measurement of blood pressure and for administration of drugs. After tracheotomy, the animals were paralyzed with intravenous infusion of 6.19 8 mg/kg pancuronium bromide and were ventilated using a respirator. The CBF was measured by the hydrogen clearance method. Briefly, an epoxy-coated platinum electrode, 300 aim in diameter, with a 1 mm portion at its tip uncoated and plated with platinum black, was placed stereotaxically in the striatum and another one in the hippocampus. The reference electrode was an Ag-AgCI electrode inserted under the skin. The rectal temperature of animals was maintained close to 37 °C.As shown in Fig. 1, administration of L DOPS (3 mg/kg, i.v.) produced a statistically significant increase in striatal blood flow as well as an elevation in mean arterial blood pressure (MABP), whereas 1 mg/kg of L DOPS produced no significant effect on CBF. These effects were long-acting. Similar results were also observed in the hip pocampus, but the flow increment was somewhat less than that in the striatum (not shown in the figure). The increases in CBF and MABP produced by L-DOPS were inhibited by about 85 and 70%, respectively, by i.v. infusion of a peripheral aromatic L

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L-threo-3,4-dihydroxyphenylserine treatment for akinesia and freezing of Parkinsonism.

Cited by 106 publications

References 0 publications

L-threo-3,4-dihydroxyphenylserine treatment for gait apraxia in parkinsonian patients.

L-threo-3,4-dihydroxyphenylserine treatment for gait apraxia in parkinsonian patients.

Inhibitory Effects of L-Threo-DOPS, an L-Noradrenaline Precursor, on Locus Coeruleus-Originating Neurons in the Caudate Nucleus

Effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS), an immediate precursor of norepinephrine, on the cerebral blood flow in rats.

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