Oral Choline Administration to Patients with Tardive Dyskinesia

Growdon, John H.; Hirsch, Madelyn J.; Wurtman, Richard J.; Wiener, W. B.

doi:10.1056/nejm197709082971002

Cited by 151 publications

(28 citation statements)

References 28 publications

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“…The doses of dopamine and norepinephrine needed to stimulate PtdEtnMeTase in our studies were thus similar to those required for the in vitro activation of adenylate cyclase in rat brain, dopamine exhibiting greater potency than norepinephrine (22,25). The effect of dopamine on phospholipid methylation appears to be receptor mediated, because it is localized in synaptosomes (Table 3) and could be-partially blocked by halo- 30 min of incubation are present in the assay mixture as free choline (1). Thus, it is possible that the rates of endogenous brain choline synthesis may also be affected by dopamine.…”

Section: Discussionmentioning

confidence: 99%

“…Prolonged exposure to dopamine receptor blockers such as haloperidol could inhibit PtdEtnMeTase activity in the basal ganglia, depressing the de novo synthesis of choline and thus diminishing acetylcholine synthesis (29). Indeed, it has been shown that therapy with choline or lecithin can ameliorate the abnormal movements of tardive dyskinesia (30,31).…”

Section: Discussionmentioning

confidence: 99%

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Dopamine stimulation of phosphatidylcholine (lecithin) biosynthesis in rat brain neurons.

Leprohon¹,

Blusztajn²,

Wurtman³

1983

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

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Rat brain synaptosomes contain enzymes, phosphatidylethanolamine N-methyltransferase(s) (EC 2.1.1.17), that catalyze the methylation of endogenous phosphatidylethanolamine to form its mono-, di-, and trimethyl (i.e., phosphatidylcholine) derivatives. We observe that the activity of these enzymes is [hepatocytes (16)]. This process is rapid and not dependent on cAMP synthesis. Little information has been available on the control of PtdEtnMeTase activity within brain neurons. We report here that catecholamine neurotransmitters, especially dopamine, enhance the activities of phosph6lipid methylating enzymes in rat brain synaptosomes. METHODSPreparation of Subcellular Fractions. Male Sprague-Dawley rats (200-300 g; Charles River Breeding Laboratories) were housed under a 12-hr/12-hr light/dark schedule (lights on, 0900-2100 hr) and had free access to water and food (Charles River chow; 22% protein, 0.018% choline). The animals were decapitated at 1000 hr, and the brains were quickly dissected on ice and homogenized in 10 vol of 0.32 M sucrose in a Potter-Elvehjem homogenizer; the homogenate was then centrifuged at 1,000 x g for 15 min to remove tissue debris and nuclei. The supernatant was layered on top of 4 ml of 1.2 M sucrose and centrifuged at 165,000 X -g for 15 min in a Beckman SW 41 Ti rotor. The resulting pellet contained mitochondria; the material at the interface of the gradient (containing the synaptosomes and myelin) was diluted to obtain approximately 0.32 M sucrose, layered on top of 4 ml of 0.8 M sucrose, and centrifuged at 165,000 X g for 15 min (17). The material at the interface, containing myelin, and the pellet, shown to contain synaptosomes by electron microscopy, were collected. In some cases, the postnuclear supernatant was centrifuged at 20,000 x g for 20 min to obtain the P2 pellet (containing synaptosomes, mitochondria, and myelin). The post-P2 supernatant was centrifuged at 100,000 X g for 60 min to obtain a microsomal pellet.PtdEtnMeTase Assay. PtdEtnMeTase activity was assayed by a modification of the method described previously (4). The standard assay medium was changed to 50 mM Tris HCl, pH 7.5/5 mM MgCl2/0.2 mM EDTA/0. 1 mM ATP and tissue preparation (0.2-0.4 mg of protein) in a final volume of 120 1.l. The effect on phospholipid [3Himethyl incorporation of omitting various components of this medium was examined (see Table 1). Norepinephrine-HCI (Sigma), dopamineHCl (Sigma), haloperidol lactate (5 mg/ml, containing 1.8 mg of methylparaben and 0.2 mg of propylparaben; a gift from McNeil, Fort Washington, PA), were added to some tubes before incubation. Reactions were started by addition of 2.5 jCi of S-adenosyl[methyl-3H]methionine (New England Nuclear; 13-15 Ci/mmol; 1 Ci = 37 GBq) to a final AdoMet concentration of 1.2-1.6 ,uM. Samples were incubated for 30 min at 37TC. Reactions were stopped by addition of 3 ml of chloroform/methanol/HCI, 100:50:1 (vol/vol). Water-soluble radioactive. materials were extracted by washing the incubation mixture with two 2-ml portions of 0....

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dopamine stimulation of phosphatidylcholine (lecithin) biosynthesis in rat brain neurons.

Leprohon¹,

Blusztajn²,

Wurtman³

1983

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

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“…Subsequent studies have shown that most patients with tardive dyskinesia respond favorably to Ch (Davis et aI., 1976;Growdon et al, 1977d;Hirsch et al, 1977b;Tamminga et al, 1977;Barbeau, 1978) and most reports have also described some improvement in Huntington's disease, although this is inconsistent (Aquilonius andEckernas, 1975, 1977;Davis et al, 1976Davis et al, , 1977aDavis et al, , 1977bGrowdon et al, 1977b;Barbeau, 1978), perhaps because the neuronal defect in Huntington's chorea prevents the effective utilization of Ch (McGeer et al, 1973;Bird and Iversen, 1974;Stahl and Swanson, 1974) or because the muscarinic receptors upon which the neurotransmitter acts have degenerated (Enna TABLE 3 -.. 14 Berger, 1978 et al, 1976;Yamamura et al, 1977). There is evidence that patients who respond to Ch can be predicted on the basis of their response to intravenous physostigmine (Davis et al, , 1977a(Davis et al, , 1977b, which is not suitable for treatment because of its short duration of action.…”

Section: Precursor Loading: the Clinical Evidence Cholinementioning

confidence: 99%

The Neurochemical Basis of Acetylcholine Precursor Loading as a Therapeutic Strategy

Jenden

1979

Brain Acetylcholine and Neuropsychiatric Disease

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“…Some studies reported beneficial effects on TD of acetylcholine precursors such as choline (Growdon et al, 1977) or lecithin (LEC) (Growdon et al, 1978;Jackson et al, 1979).…”

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confidence: 99%

Lithium and lecithin in tardive dyskinesia: An update

Volavka¹,

O’Donnell²,

Muragali³

et al. 1986

Psychiatry Research

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Document VersionPublisher's PDF, also known as Version of Record (includes final page, issue and volume numbers)Please check the document version of this publication:• A submitted manuscript is the author's version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Abstract. Psychiatric inpatients with tardive dyskinesia (TD) were treated with either lithium alone (n=9) or with a combination of lithium and lecithin (n = 9) for 5 weeks in a double-blind, placebo-controlled experiment.A statistically significant but clinically unimportant improvement of TD occurred during both treatments. The addition of lecithin to lithium had no effect.

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Oral Choline Administration to Patients with Tardive Dyskinesia

Cited by 151 publications

References 28 publications

Dopamine stimulation of phosphatidylcholine (lecithin) biosynthesis in rat brain neurons.

Dopamine stimulation of phosphatidylcholine (lecithin) biosynthesis in rat brain neurons.

The Neurochemical Basis of Acetylcholine Precursor Loading as a Therapeutic Strategy

Lithium and lecithin in tardive dyskinesia: An update

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