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PubMed1993

Renal dopamine excretion in healthy volunteers after oral ingestion of L-dopa.

L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L-Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion.

Adult↗
PubMed1974

The cardiovascular effects of L-dopa in the pithed rat.

1 L-DOPA (1-2 mg i.v.) in the pithed rat reduced the arterial and increased the venous pressure responses to noradrenaline.2 Infusions of dopamine (4-8 mug kg(-1) min(-1)) and noradrenaline (500 ng kg(-1) min(-1)) also reduced the pressor responses to noradrenaline. The pressor response did not recover after stopping dopamine infusions, but it usually did so after stopping noradrenaline infusions.3 The effect of L-DOPA on the response to noradrenaline was prevented by the prior injection of the dopa decarboxylase inhibitor NSD 1024.4 The prior injection of the dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate, only partially prevented the effect of L-DOPA on pressor responses to noradrenaline.5 The perfusion of noradrenaline (400 ng kg(-1) min(-1)) together with Krebs solution (10 ml/min) through an organ bath containing an isolated aortic strip, depressed the response of the strip to doses of noradrenaline after the infusion was stopped. Infusions of dopamine (0.5-8.0 mug kg(-1) min(-1)) had a similar effect. Fifteen minutes after adding L-DOPA (0.5 mg) to the bath and 10 min after washing it out, the response to noradrenaline was depressed in three out of four experiments.6 Infusions of noradrenaline (1 mug kg(-1) min(-1)) in an isolated heart perfused by Langendorf's method blocked the response to injected noradrenaline whilst perfusion was in progress. Infusions of dopamine (4-8 mug kg(-1) min(-1)) or of L-DOPA (200 mug kg(-1) min(-1)) did not have this effect.7 It is concluded that the effect of L-DOPA on pressor responses to noradrenaline in the pithed rat are mediated by its conversion to dopamine and noradrenaline.

Animals↗
PubMed1986

Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L-dopa without modifying its cardiovascular effects.

The potential of a new, potent, irreversible and selective inhibitor of monoamine oxidase type B, (E)-2-(3,4-dimethoxyphenyl)-3-fluorallyamine (MDL 72145), to augment the effects of L-DOPA in an animal model which reproduces the biochemical defect of Parkinson's disease has been evaluated. In rats bearing unilateral 6-hydroxydopamine lesions of the nigro-striatal dopamine pathways, both MDL 72145 and clorgyline, a selective inhibitor of MAO A, augmented the contralateral turning response to L-DOPA combined with carbidopa. The potential of inhibitors of MAO to interact adversely in the periphery with L-DOPA was investigated in the pithed rat; L-DOPA was given either intravenously or intraduodenally. Clorgyline consistently potentiated L-DOPA when given 18 h before testing. Neither MDL 72145 nor the selective inhibitor of MAO B, L-deprenyl, augmented the cardiovascular effects of intraduodenally administered L-DOPA. The data provide no reason to suppose that MDL 72145 would be very different in clinical use from L-deprenyl which is both effective and well-tolerated as an adjunct to the L-DOPA-based therapy of Parkinson's disease.

Allylamine↗
PubMed1994

Human TRP-1 has tyrosine hydroxylase but no dopa oxidase activity.

Human TRP-1 has been immunopurified from normal human melanocytes cultured from black neonatal subjects and used to investigate the catalytic function of TRP-1 for the two substrates, L-tyrosine and L-DOPA. Immunopurified TRP-1 did not demonstrate DOPA staining on SDS/PAGE nor DOPA oxidase (DO) activity with either routine or modified assays. The purified TRP-1 also demonstrated no tyrosine hydroxylase (TH) activity using the routine Pomerantz assay. However, there was apparent TH activity exhibited by immunopurified TRP-1 under conditions with low tyrosine concentration (< or = 0.8 microCi/ml of 3H-tyrosine), prolonged incubation time (i.e., overnight) and in the absence of the cofactor L-DOPA. Using these latter specific conditions, TH activity was also detected in cell lysates from a tyrosinase-negative albino melanocyte line which exhibited no TH activity with the routine Pomerantz assay. In addition, TH activity under low substrate assay conditions was not exhibited in a melanocyte line derived from a TRP-1 deficient, Brown albino individual. However, the absence of TH in this Brown albino cell line could be compensated for by the addition of L-DOPA to the assay. These results suggested that TRP-1 has some tyrosine hydroxylase but no DOPA oxidase activity. We propose that one function of TRP-1 is to modulate tyrosinase activity by making DOPA available as a cofactor to perpetuate the initial steps in melanogenesis.

Cells, Cultured↗
PubMed1990

MPTP-induced hypoactivity in mice: reversal by L-dopa.

Three experiments were performed to study the subchronic effects of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 2 x 40 mg/kg subcutaneously two weeks before testing) in C57 BL/6 mice upon spontaneous motor activity and the reversal of the long-term behavioural changes by acute treatment with L-Dopa. Mice treated with MPTP showed a drastic reduction of striatal dopamine levels (-88%) associated with reductions of all three parameters of spontaneous motor activity, i.e. locomotion, rearing and total activity, during both the initial, exploratory, stage (first 90 min), and later stages of the 3- or 4-hr test periods. L-Dopa (5-80 mg/kg subcutaneously) injected 60 min. after the start of testing dose-dependently improved all three parameters studied in MPTP treated mice with 10 mg/kg being the lowest dose causing a significant effect, while doses above 20 mg/kg caused hyperactivity. During the initial period, rearing activity in MPTP mice was to a variable degree suppressed by the L-Dopa treatment (20-80 mg/kg); these reductions were followed by enormous increases in motor activity by the 40 mg/kg (locomotion) and 80 mg/kg (total activity) L-Dopa groups. Both the degree and duration of the L-Dopa-induced hypoactivity for locomotor behaviour increased dose-dependently in control mice. No suppressive effects of L-Dopa were obtained for total activity in control mice, although the 80 mg/kg L-Dopa doses evoked hyperactivity for up to 90 min. following treatment for both locomotion and total activity.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1977

Quantitative evaluation of the blood-brain barrier capacity to form dopamine from circulating L-DOPA.

The ability of the blood-brain barrier to form dopamine from increasing doses of systemically administered L-DOPA has been studied in rats by a combination of chemical determination of dopamine, and histochemical and cytofluorometric measurements of L-DOPA and dopamine. The break-through of L-DOPA from the circulation into the brain parenchyma via the enzymatic blood-brain barrier was estimated by comparing the amount of newly formed dopamine in the caudate nucleus-putamen and in the cerebellum. The capillaries were found to efficiently trap L-DOPA in their walls, and an upper limit was reached (at an administered i.p. dose of 100 mg/kg of L-DOPA). It could be estimated that approximately 3% of the total dose of L-DOPA given was decarboxylated by the blood-brain barrier. The possible influence by the regional differences in perfusion of the two regions seen after administration of L-DOPA was ruled out in measurements of local cerebral blood flow using the 14C-ethanol technique.

Animals↗
PubMed1992

Decarboxylation of L-dopa in the rat isolated vascularly perfused small intestine: contribution to systemic elimination and dose-dependent first pass effect.

The contribution of the rat small intestine to systemic and presystemic elimination of L-dopa was studied. When L-dopa was administered into the vascular perfusate, a systemic extraction ratio of 0.38 was found, the major part being decarboxylated to dopamine. The intestinal L-dopa clearance was estimated to be 17.1 mL min-1 kg-1. Thus, L-dopa intestinal clearance in rat represents up to at least 20% of the total body clearance. After luminal administration of L-dopa 83-88% of the administered dose was absorbed within 60 min. The total amount of L-dopa appearing in the vascular perfusate increased more than proportionally to the increase in the dose. In contrast, the amount of dopamine increased less than proportionally to the dose. As a result, the intestinal first pass appeared to be strongly dose-dependent. Since the total percentage absorbed from the lumen was independent of the administered dose and the total amount that appeared in the vascular perfusate increased linearly with the dose, the dose dependency was probably due to saturation of intestinal L-dopa decarboxylation.

Animals↗
PubMed1971

Kantamaneni BD, Curzon G:Comparison of benefit from L-dopa in Parkinsonism with increase of amine metabolites in the CSF.

Homovanillic acid (HVA) and 5-hydroxy indole acetic acid (5-HIAA) concentrations have been estimated in the cerebrospinal fluid (CSF) of 16 and 18 patients respectively with Parkinsonism both before and during treatment with l-dopa. The rise of HVA correlated with dose of l-dopa. An increase of HVA concentration to less than 0·10 μg/ml. was associated with little or no clinical improvement. The five patients with the greatest increase of HVA concentration/g l-dopa showed little or no improvement from treatment and four of these patients had normal pre-treatment HVA and 5-HIAA. In those patients who responded well to l-dopa the CSF HVA/g l-dopa was intermediate between that of these two groups. It is suggested that change in HVA content of CSF during l-dopa treatment might be of value in the prediction of response to l-dopa.

Aged↗
PubMed1973

Quantitative study of the effect of L-dopa and phenoxybenzamine on the rigidity of Parkinson's disease.

The static and dynamic components of the tonic stretch reflex and shortening reactions have been studied in biceps brachii, triceps, hamstrings, and quadriceps muscles of 19 patients with Parkinson's disease before and during L-dopa therapy. Clinical improvement during L-dopa administration correlated with a reduction in the dynamic component of the tonic stretch reflex in biceps, triceps, and quadriceps but not the hamstrings muscle, and with the static component of the tonic stretch reflex in biceps and triceps but not quadriceps and hamstrings muscles. The only shortening reaction consistently reduced during the L-dopa treatment period was the dynamic shortening reaction of the triceps muscle. The responses of the stretch reflexes to changes in muscle length were not altered by L-dopa therapy. In severely disabled patients the hamstrings and quadriceps stretch reflexes were maximal in a position of partial flexion of the knee joint and this response to muscle length was not altered in these patients despite a dramatic lessening of rigidity in some patients. Shortening reactions commonly remained in some patients after the stretch reflex of the antagonistic muscle was abolished by L-dopa therapy. The administration of phenoxybenzamine to patients being treated with L-dopa reduced the different components of rigidity more than L-dopa alone, and the responses were consistent with phenoxybenzamine suppressing predominantly the descending noradrenergic pathway.

Aged↗
PubMed2001

Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors.

PURPOSE: To evaluate fluorine 18 (18F) dopa positron emission tomography (PET) in comparison with established imaging procedures in gastrointestinal carcinoid tumors. MATERIALS AND METHODS: After evaluation of the normal distribution of 18F dopa, 17 patients with histologically confirmed tumors were examined with 18F dopa PET. Results of 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) PET, somatostatin-receptor scintigraphy, and morphologic imaging (computed tomography and/or magnetic resonance imaging) were available for all patients. Results of the procedures were evaluated by two radiologists and two nuclear medicine specialists, whose consensus based on all available histologic, imaging, and follow-up findings was used as the reference standard. RESULTS: Ninety-two tumors were diagnosed: eight primary tumors, 47 lymph node metastases, and 37 organ metastases. 18F dopa PET led to 60 true-positive findings (seven primary tumors, 41 lymph node metastases, 12 organ metastases); FDG PET, 27 (two primary tumors, 14 lymph node metastases, 11 organ metastases); somatostatin-receptor scintigraphy, 52 (four primary tumors, 27 lymph node metastases, 21 organ metastases); and morphologic imaging, 67 (two primary tumors, 29 lymph node metastases, 36 organ metastases). This resulted in the following overall sensitivities: 18F dopa PET, 65% (60 of 92); FDG PET, 29% (27 of 92); somatostatin-receptor scintigraphy, 57% (52 of 92); morphologic procedures, 73% (67 of 92). Although the morphologic procedures were most sensitive for organ metastases, 18F dopa PET enabled best localization of primary tumors and lymph node staging. CONCLUSION: 18F dopa PET is a promising procedure and useful supplement to morphologic methods in diagnostic imaging of gastrointestinal carcinoid tumors.

Adult↗
PubMed1980

Blood-brain barrier transport and cerebral utilization of dopa in living monkeys.

[18F]fluoro-dopa, DL-3,4-dihydroxy-5-[18F]fluorophenylalanine, a tracer for dopa, was injected intravenously into cynomolgus monkeys anesthetized with enflurane, and the appearance of 18F in the head and the disappearance of 18F from the blood were each measured continuously for 10 min with simple gamma-ray detectors. A three-compartment explanatory model was used to derive fractional rate constants for the forward flux of L-dopa into the endothelium of the brain capillaries from the blood (1.54 +/- 0.37 min-1), the back flux of dopa and/or its metabolites to the blood from the endothelium (0.67 +/- 0.05 min-1), the formation of dopamine from dopa (0.20 +/- 0.04 min-1), and the destruction of dopamine (0.04 +/- 0.02 min-1). It was also shown that only one-fifth of the dopa that entered the endothelium was available for dopamine synthesis in neurons. It was concluded that the technique described could be extended to man and used to investigate the role of dopa and dopamine in the control of mood and locomotion.

Animals↗
PubMed2000

L-Dopa uptake and dopamine production in proximal tubular cells are regulated by beta(2)-adrenergic receptors.

This study assessed the role of adrenergic receptors on the regulation of the uptake of L-dopa and the production of dopamine by renal tubular cells. Scatchard analysis showed two L-dopa uptake sites with different affinities (K(m) 0.316 vs 1.53 microM). L-Dopa uptake was decreased by the nonselective adrenergic agonists epinephrine or norepinephrine (40%), by the beta-selective agonist isoproterenol or the beta(2)-selective agonist terbutaline (60%), but not by alpha-selective agonists (all 1 microM). The effect of norepinephrine, isoproterenol, or terbutaline was unaffected by addition of the beta(1)-antagonist atenolol, abolished by ICI-118, 551, a beta(2)-antagonist (both 0.1 microM), and mimicked by the addition of dibutyryl-cAMP (1 microM). Preincubation with terbutaline decreased the number of high-affinity uptake sites (V(max) = 1.10 +/- 0.3 vs. 0.5 +/- 0.1 pmol. mg protein(-1). min(-1)) without changing their affinity. Norepinephrine or terbutaline decreased dopamine production by isolated cells, and this effect was abolished by ICI-118,551 (0.1 microM). In vivo administration of ICI-118,551 reduced the urinary excretion of L-dopa and increased the excretion of 3,4-dihydroxyphenylacetic acid without significant changes in plasma L-dopa concentrations. These results demonstrate that stimulation of beta(2)-adrenergic receptors decreases the number of high-affinity L-dopa uptake sites in isolated tubular cells resulting in a reduction of the uptake of L-dopa and the production of dopamine and provide evidence for the presence of this mechanism in the intact animal.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Biopterin synthesis defect. Treatment with L-dopa and 5-hydroxytryptophan compared with therapy with a tetrahydropterin.

We have identified a generalized deficiency of monoamine neurotransmitters in a patient with a defect in biopterin synthesis. Neurotransmitter precursors (L-3,4-dihydroxyphenylalanine [L-dopa]; 5-hydroxytryptophan [5-HTP] and a tetrahydropterin [6-methyltetrahydropterin (6MPH4)] were investigated for their ability to normalize monoamine neurotransmitter metabolism. Before treatment, the concentrations of dopamine (DA), norepinephrine, epinephrine, and six monoamine metabolites were very low or undetectable in plasma, cerebrospinal fluid, or urine. L-Dopa and 5-HTP replacement was begun at age 7 mo. This therapy generally corrected the deficiency of monoamines and their metabolites, and improved neurological development until the age of 25 mo. Despite these benefits, the intermittent administration of L-dopa could not produce a stable improvement of acute neurological function or DA metabolism. In the 3 h after L-dopa administration, plasma DA and the motor activity and alertness of the patient rose and fell in parallel. Doses of L-dopa that were clinically optimal produced normal plasma levels of norepinephrine and epinephrine, but excessive concentrations of DA and its metabolites. Furthermore, the clinical and biochemical effects of L-dopa were inhibited by phenylalanine and 5-HTP, respectively, demonstrating that these amino acids have antagonistic pharmacological effects. Physiological correction of the monoamine deficit and the hyperphenylalaninemia of this disorder was attempted at age 35 mo using high doses (8-38 mg/kg per d) of 6MPH4. 6MPH4, a synthetic analogue of tetrahydrobiopterin, controlled the hyperphenylalaninemia. Significant concentrations of 6MPH4 were obtained in the cerebrospinal fluid; no neurological improvement or stimulation of monoamine synthesis in the central nervous system was detected. These findings indicate the complexity in replacement therapy with L-dopa and 5-HTP, but suggest that this treatment may be partially effective in biopterin-deficient patients who are unresponsive to high doses of tetrahydropterins.

5-Hydroxytryptophan↗
PubMed2002

PET study of [(18)F]6-fluoro-L-dopa uptake in neuroleptic- and mood-stabilizer-naive first-episode nonpsychotic mania: effects of treatment with divalproex sodium.

OBJECTIVE: Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and mood-stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring [(18)F]6-fluoro-L-dopa ([(18)F]DOPA) uptake in the striatum with positron emission tomography (PET). METHOD: Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [(18)F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6 weeks after beginning treatment with divalproex sodium monotherapy. [(18)F]DOPA uptake rate constants (K(i) values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function. RESULTS: No significant differences in [(18)F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, [(18)F]DOPA rate constants were significantly reduced in the patients and were lower in the patients than in the comparison subjects. CONCLUSIONS: Although presynaptic dopamine function as reflected by [(18)F]DOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.

Adult↗
PubMed1975

Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine.

One gram of L-dopa was administered orally to 12 male control subjects and induced an increase of growth hormone (GH) secretion. The L-dopa-induced GH response was inhibited by an intravenous infusion of pyridoxine, but pyridoxine did not inhibit the GH response to hypoglycemia. Chlorpromazine also inhibited L-dopa-induced GH stimulation. Glucose concentrations were unaffected by L-dopa, chlorpromazine, and pyridoxine administration in these subjects. The mechanism of the suppressed L-dopa-induced GH response by pyridoxine appears to be mediated by peripheral accleration of the conversion of L-dopa to dopamine, while that of chlorpromazine appears to be mediated through hypothalamic centers. Pyridoxine and chlorpromazine should be added to the list of other factors affecting the response to L-dopa-induced GH stimulation

Adult↗
PubMed1995

Cardiotoxicity of catecholamines after application of L-DOPA in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR).

In order to estimate the role of the sympatho-adrenal system as a trigger in cardiovascular mortality risk after L-DOPA administration in patients with Parkinsons disease we performed the following experiments in normotensive Wistar-Kyoto-rats (WKY) and spontaneously hypertensive rats (SHR). L-DOPA was given orally in increasing doses (30, 100, 300 mg/kg b.w.). Haemodynamic parameters (BP, HR) were measured by tail cuff plethysmography and catecholamine concentrations in tissues assayed by high pressure liquid chromatography. Stressful situations were induced by experimental myocardial infarction. After administration of L-DOPA a dose-dependent increase in blood pressure in both WKY and SHR was observed with a prolongation in SHR. Significantly increased concentrations of dopamine in the hearts were measured in both strains. Noradrenaline stores in the heart of WKY were more filled than in the heart of SHR. Only in SHR high adrenaline concentration in the adrenal medulla were measured after L-DOPA administration. Circulating adrenaline concentrations were significantly enhanced after myocardial infarction in WKY and could be further elevated by pretreatment with L-DOPA. From the results obtained it is concluded that L-DOPA administration in WKY and SHR leads to exaggerate synthesis and massive release of catecholamines and in consequence to an enhanced cardiovascular mortality risk due to cardiotoxicity of catecholamines. It can be extrapolated that increased cardiovascular mortality risk seen in Parkinson patients treated with L-DOPA and benzerazide is probably associated with increased synthesis and release of catecholamines during stressful situations.

Animals↗
PubMed1989

Evaluation of hypothalamic-pituitary function in a combination of tests with four hypothalamic releasing hormones and L-dopa in normal subjects and in patients with hypothalamic and/or pituitary disorders.

Hypothalamic-pituitary function was evaluated in a combination of tests with four hypothalamic releasing hormones (4RHs) and L-dopa in normal subjects and in patients with hypothalamic and/or pituitary disorders. Plasma concentrations of anterior pituitary hormones (GH, ACTH, TSH, PRL, LH and FSH) were measured before and after simultaneous iv administration of GHRH, CRH, TRH and LHRH. In addition, changes in the plasma levels of GHRH and GH were investigated before and after oral administration of L-dopa. Normal subjects showed appreciable responses to both tests. In five patients with hypothalamic disorders, the response of plasma anterior pituitary hormones varied, but plasma GHRH and GH did not respond to L-dopa. Patients with idiopathic and postpartum hypopituitarism showed low response to 4RHs or none at all, but L-dopa evoked a normal GHRH response in 2 of the 4 cases having no GH response. In the patients with hypopituitarism due to resection of a pituitary tumor, the response of anterior pituitary hormones to 4RHs was low, and L-dopa administration induced a normal GHRH and low GH response in 5 out of the 7 cases. After 4RHs administration, the patients with ACTH deficiency syndrome showed different patterns of impaired ACTH secretion, and isolated, combined or limited ACTH reserve. Seven patients with anorexia nervosa showed exaggerated GH, delayed TSH and FSH, low ACTH and LH, that is, normal PRL response to 4RHs, but no response of plasma GHRH or GH to L-dopa, suggesting the presence of hypothalamic dysfunction. These results indicate that the combination of the 4RHs test and L-dopa test is a simple and useful means for evaluating hypothalamic-pituitary function by measuring the response of plasma GHRH and six anterior pituitary hormones in the patients with endocrine disorders.

Adolescent↗
PubMedDate not supplied

The neuroregulatory properties of L-DOPA. A review of the evidence and potential role in the treatment of Parkinson's disease.

Accumulating evidence suggests that L-dihydroxyphenylalanine (L-DOPA) has neurotransmitter-like and/or neuromodulatory properties in the CNS. Such evidence is based on a wide range of findings including the existence of specific L-DOPAergic neurons in several regions of the CNS, neurotransmitter-like characteristics and specific pharmacological effects. This review attempts to outline the main evidence for this conception and to relate such findings to L-DOPA treatment effects in Parkinson's disease. In this context L-DOPA in itself has been shown to potentiate D2 receptor-mediated effects, inhibit acetylcholine release and increase the release of L-glutamate, neuropharmacological effects which can be linked to treatment side-effects in advanced Parkinson's disease. It is suggested that supersensitive L-DOPA-mediated effects contribute to the pathogenesis underlying L-DOPA-induced motor complications in advanced Parkinson's disease. However, since specific L-DOPA receptors have yet to be identified, the assessment of the relative importance of L-DOPA-mediated effects in this clinical context must be regarded as incomplete.

Central Nervous System↗