Predicting the Response to Levodopa

Woert, MelvinH. Van; Weintraub, MichaelI.

doi:10.1016/s0140-6736(71)91409-7

Cited by 9 publications

(3 citation statements)

References 16 publications

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“…Some studies have resported that the HVA concentration was significantly correlated with the clinical severity, but not with the responsiveness to L-dopa (Weiner et al, 1973;Chase et al, 1972), while in other studies the HVA concentration was not correlated with the clinical severity, but with the responsiveness to L-dopa (Van Woert et al, 1971;Jequier et al, 1972;Bianchine et al, 1976;Gumpert et al, 1973;Cunha et al, 1983;Lakke et al, 1971). A significant positive correlation between the HVA concentration and improvement scores following L-dopa has also been reported (Bowers and Van Woert, 1972).…”

Section: Discussionmentioning

confidence: 98%

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Tohgi

Abe

Takahashi

et al. 1993

J Neural Transm Gen Sect

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We correlated monoamine concentrations in the cerebrospinal fluid from de novo (untreated) patients with Parkinson's disease with their clinical symptoms and therapeutic outcome after two years of L-dopa with/without other anti-parkinson medication. A significant correlation was found between the severity of some parkinsonian symptoms and the reduction in particular monoamines: Hoehn and Yahr's stage with dopamine, norepinephrine, and homovanillic acid: rigidity with dopamine; akinesia with dopamine and norepinephrine; freezing of gait with norepinephrine; and dementia with dopamine and homovanillic acid. Tremor had no correlations with the concentrations of the monoamines measured. Patients with dementia had a significantly increased level of epinephrine concentrations. Insufficient therapeutic responses of individual symptoms were associated with significantly decreased concentrations of particular monoamines before treatment: Hoehn and Yahr's stage with norepinephrine and epinephrine; akinesia with homovanillic acid and 5-hydroxyindoleacetic acid; and freezing of gait with dopamine, norepinephrine, homovanillic acid, and 5-hydroxyindoleacetic acid. These results suggest a significant correlation between the reduction in particular monoamines and the severity of some parkinsonian symptoms and their subsequent responses to L-dopa.

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Section: Discussionmentioning

confidence: 98%

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Tohgi

Abe

Takahashi

et al. 1993

J Neural Transm Gen Sect

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“…Large doses of the acetyicholinesterase inhibitor, physostigmine, produce tremors in animals, presumably by increasing acetylcholine levels in the basal ganglia (Frances & Jacob, 1971). In patients with Parkinson's disease, physostigmine aggravates tremor, rigidity, and hypokinesia at a dose which has no neurological effects in normal subjects (Duvoisin, 1967;Weintraub & Van Woert, 1971;Van Woert & Weintraub, 1971). Anticholinergic drugs and L-dihydroxyphenylalanine (L-DOPA) clinically improve this disease and reduce or prevent the adverse neurological effects of physostigmine (Duvoisin, 1967;Weintraub & Van Woert, 1971;Van Woert & Weintraub, 1971).…”

mentioning

confidence: 99%

“…In patients with Parkinson's disease, physostigmine aggravates tremor, rigidity, and hypokinesia at a dose which has no neurological effects in normal subjects (Duvoisin, 1967;Weintraub & Van Woert, 1971;Van Woert & Weintraub, 1971). Anticholinergic drugs and L-dihydroxyphenylalanine (L-DOPA) clinically improve this disease and reduce or prevent the adverse neurological effects of physostigmine (Duvoisin, 1967;Weintraub & Van Woert, 1971;Van Woert & Weintraub, 1971). If the hypersensitivity to physostigmine in Parkinson's disease is due to decreased brain dopamine (Ehringer & Hornykiewicz, 1960), drugs whilch alter dopamine metabolism might also affect the neurological response to physostigmine.…”

mentioning

confidence: 99%

Modification of the tremorigenic activity of physostigmine

Ambani

Woert

1972

British J Pharmacology

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Drugs which reduce central catecholamine activity increased the tremorigenic action of physostigmine (025 mg/kg) in the rat. The potentiation of physostigmine tremor induced by these neuroleptic drugs was quantitated by measuring the ratio of post-to prephysostigmine motor activity; this ratio may be a useful index of catecholamine/cholinergic balance. Of the compounds tested, chlorpromazine HCI (15 mg/kg) and reserpine (10 mg/ kg) had the greatest potentiating effect on the tremor-producing action of physostigmine. L-DOPA (500 mg/kg) reduced the tremor induced by physostigmine in rats pre-treated with reserpine, but not in rats pre-treated with chlorpromazine.Normal extrapyramidal function may depend upon a sensitive balance between inhibitory dopaminergic neurones and excitatory cholinergic fibres in the basal ganglia (McGeer, Boulding, Gibson & Foulkes, 1961;Barbeau, 1962). Large doses of the acetyicholinesterase inhibitor, physostigmine, produce tremors in animals, presumably by increasing acetylcholine levels in the basal ganglia (Frances & Jacob, 1971). In patients with Parkinson's disease, physostigmine aggravates tremor, rigidity, and hypokinesia at a dose which has no neurological effects in normal subjects (Duvoisin, 1967;Weintraub & Van Woert, 1971;Van Woert & Weintraub, 1971). Anticholinergic drugs and L-dihydroxyphenylalanine (L-DOPA) clinically improve this disease and reduce or prevent the adverse neurological effects of physostigmine (Duvoisin, 1967;Weintraub & Van Woert, 1971;Van Woert & Weintraub, 1971). If the hypersensitivity to physostigmine in Parkinson's disease is due to decreased brain dopamine (Ehringer & Hornykiewicz, 1960), drugs whilch alter dopamine metabolism might also affect the neurological response to physostigmine.Recent studies in our laboratory demonstrated that serial intracisternal injections of 6-hydroxydopamine in dogs produced hypokinesia and frequently rigidity and tremor which were aggravated by intravenous physostigmine and reversed by L-DOPA and benztropine (Van Woert, Amibani & Bowers (1972) in press). We suggested that the physostigmine hypersensitivity induced' by 6-hydroxydopamine was due to the degeneration of catecholamine containing neurones produced by this amine.This communication describes the results of further experiments in rats designed to correlate the tremorigenic activity of physostigmine with drug-induced changes in catecholamine metabolism. We were particularly interested in the effect of drugs which, produce Parkinsonism such as reserpine, phenothiazines, and haloperidol on physostigmine tremor.Methods. -152 Sprague-Dawley rats weighing 180 to 220 g were used in the experiments. Tremor and motor activity were measured on a 501 activity platform (Lafayette Instruments, Lafayette, Indiana) set at a sensitivity adjustment of 10 which minimized counts due to exploratory movements, but still recorded tremor. Two rats were placed on the activity platform at one time for each measurement. After a 3 min period to permit the rats to familiarize themsel...

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The Pharmacology of Levodopa in Treatment of Parkinson’s Disease: An Update

LeWitt¹

1989

Drugs for the Treatment of Parkinson’s Disease

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Predicting the Response to Levodopa

Cited by 9 publications

References 16 publications

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Modification of the tremorigenic activity of physostigmine

The Pharmacology of Levodopa in Treatment of Parkinson’s Disease: An Update

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