Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DOPA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources
PubMed1977

L-dopa-induced hypotension: depression of spinal sympathetic neurons by release of 5-hydroxytryptamine.

In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.

5-Hydroxytryptophan↗
PubMed1985

Pathophysiology of L-dopa-induced abnormal involuntary movements.

Among the various deficiencies in neurotransmitters and neuropeptides in the brains of patients with Parkinson's disease, the loss of dopamine (DA) is implicated in a major way in the occurrence of L-dopa-induced abnormal involuntary movements (AIMs). Whatever the clinical pattern, they are triggered by drugs which stimulate DA transmission and can be modified by DA agonists and antagonists. They occur when DOPA plasma concentrations, and thus central DA receptor stimulation, reach a critical level. They are observed in patients with severely damaged central DA neurons, but involvement of other neurotransmitter-containing cells cannot be excluded. L-Dopa-induced AIMs have clinical and somatotopic characteristics, which vary from patient to patient. One might speculate that variable damage to DA neurons, associated or not with other neurotransmitter-containing cells in the affected brain structures, causes these differences in AIM patterns. By analogy with behavioral experiments in animals, the hypersensitivity of DA receptors observed in the basal ganglia of parkinsonian patients post mortem might reasonably be considered to mediate L-dopa-induced AIMs. However, the role of various subtypes of DA receptors or of changes in DA metabolism in the cell bodies and dendrites (substantia nigra) or nerve terminals (striatolimbic areas) must also be considered. In brief, the features, topography, and timing of L-dopa-induced AIMs are dependent upon alterations of the functional expression of striatal DA output, which is not yet well understood.

Brain↗
PubMed1980

Kinetics of L-DOPA metabolism in the caudate nucleus of cats with ventrotegmental lesions.

Sixteen days after a unilateral lesion of the ventromedial tegmentum (VMT) of the midbrain, adult cats received an intravenous dose of L-DOPA (20 mg/kg), and the caudate nucleus from each hemisphere was removed at various time intervals thereafter. In the caudate nucleus contralateral, to the VMT lesions, DA levels reached 200% of control values within 15 min, and maintained this elevation for at least 2 hours. DA levels in the caudate nucleus ipsilateral to the VMT lesion were much lower than contralateral values; however, they were much higher than those of non-DOPA treated animals with comparable lesions. DA levels in the caudate nucleus of the lesioned hemisphere were directly related to the remaining DOPA decarboxylase activity. The striatal serotonin concentrations were unchanged after L-DOPA, but an increase in 5-hydroxyindoleacetic acid levels was observed. From these results, we conclude that, (i) in cats with nigrostriatal tract lesions after low doses of L-DOPA comparable to those given to patients with Parkinson's disease, the bulk of the newly formed DA in the caudate nucleus is contained in nigrostriatal neurons, and (ii) there exists an inverse relationship between the ability of the caudate to synthesize DA and the severity of the nigrostriatal tract lesion.

Animals↗
PubMed1994

Biotransformation of locally applied L-dopa in the corpus striatum of the hemi-parkinsonian rat studied with microdialysis.

Microdialysis was used to study the biotransformation of L-dopa in intact and denervated striata of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Microdialysis probes were placed in the intact and in the denervated striatum. Observations were then made on freely moving rats. Extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) were monitored before, during and after the local administration of L-dopa via the microdialysis probe for 20 min. A dose-dependent increase in extracellular dopamine levels was seen in intact striatum after application of L-dopa in concentrations ranging between 100 nmol/l and 10 mumol/l. In the denervated striatum, the severity of the lesion influenced dopamine formation, so that no dose-effect relation could be established. The effects of the continuous intra striatal infusion of nomifensine, tetrodotoxin or benserazide on the L-dopa-induced dopamine outflow revealed that in the intact striatum this dopamine release is mainly voltage dependent. It was concluded that in the denervated striatum other cells of non-neuronal origin and containing aromatic L-amino acid decarboxylase make a major contribution to the increase in extracellular dopamine levels. Furthermore, L-dopa itself shows no dopamine-releasing properties, at least under the present experimental conditions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Antispastic effects of L-dopa.

Antispastic effects of the noradrenaline and dopamine precursor l-3,4-dihydroxyphelanine (L-dopa) were investigated in 11 subjects in which exaggerated stretch reflexes developed after spinal cord injuries. The effects were evaluated from changes in the electromyographic (EMG) response of the quadriceps muscle during tendon jerks evoked by standardized taps over the patellar tendon, in clonus and in resistance to passive movements of the limb. After administration of L-dopa, EMG responses occurring 30-150 ms after the tendon tap decreased to about 50% of control, and clinical tests revealed a marked decrease in the resistance to muscle stretches and in the degree of clonus. The effects were maximal within about 1 h. The depressive actions of L-dopa are interpreted as being exerted primarily at the spinal level, since they were evoked in paraplegics and tetraplegics. The results support the previous hypothesis that group II muscle afferents contribute to.the exaggerated stretch reflex in spastic patients because L-dopa depresses transmission from group II but not from group I muscle afferents. They also indicate the possibility of using L-dopa in the treatment of spastic patients.

Adolescent↗
PubMed1989

Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells.

The toxicity and selectivity of 3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the melanin pathway, broadly paralleled that of L-dopa in a panel of human melanoma cell lines sensitive or resistant to the latter drug. A human retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both catechols were associated with inhibition of DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of dopa. Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the manganese or copper/zinc forms of superoxide dismutase, or in iron content and iron-binding capacity. Catechol toxicity was inhibited by the hydrogen peroxide scavenging agents pyruvate and methaemoglobin. Sensitivity to catechols did not correlate with melanin or tyrosinase content, rate of incorporation of tyrosine or dopa, intracellular levels of phenylalanine or tyrosine, or binding of a new monoclonal antibody directed against a melanosomal protein. These results indicate that DHBA and dopa exhibit selective toxicity for neural crest tumor cells independently of the melanisation pathway and of the superoxide scavenging system.

Cell Cycle↗
PubMed1990

Immunohistochemistry of endogenous L-DOPA in the rat posterior hypothalamus.

The aim of this work was to study L-DOPA-containing neuronal structures of the rat posterior and dorsal hypothalamus by means of immunohistochemistry using antiserum against glutaraldehyde conjugated L-DOPA. Aspects and distribution of L-DOPA immunoreaction among cells of the supramammillary nucleus and the A11, A13c and A13 cell groups are described and compared to dopamine immunoreactivity, mainly through a double colored labelling procedure employing a color modification of the DAB reaction by metallic ions. Differences between L-DOPA and dopamine stainings within cell groups as the presence of cells with predominant or exclusive L-DOPA coloration are tentatively explained under the light of previous findings using immunohistochemistry of catecholamines synthesizing enzymes and catecholamines histofluorescence.

Animals↗
PubMed1975

[Effects of alpha-methyl-dopa on new born kitten sleep. Behavioral evolution during the first month post-birth (author's transl)].

The paradoxical sleep (PS)-suppressing effect of alpha-methyl-Dopa was studied in kittens at birth. The new burn animal received daily injections of alpha-methyl-Dopa during the 2 first weeks of life. States of sleep were studied during the treatment (days 1 to 14) and after administration of the drug way halted (days 15 and 16). Daily injections of alpha-methyl-Dopa induce an average PS-deprivation of 72%. This deprievation is compensated for by a significant increase in quiet sleep (QS)-rate which is found to be up to 3.5 times that of kittens not receiving alpha-methyl-Dopa. A progressive return of PS-ratio to normal, without PS rebound, is observed after drug administration ceases. Alpha-methyl-Dopa produces a sedative effect on the kitten which remains relatively hypotonic during the treatment. Behavioural studies carried out over the first month after birth show no significant delay in the ponderal growth nor in the acquisition of stereotyped behaviour patterns. However motor coordination is delayed 2 weeks in these kittens.

Aging↗
PubMed1977

Relationship between tardive dyskinesia, L-Dopa-induced hyperkinesia and parkinsonism.

In a study of 16 psychotic patients with neuroleptic-induced tardive dyskinesia and 16 patients with Parkinson's disease and L-Dopa-induced hyperkinesia it was found that (1) tardive dyskinesia, compared to L-Dopa hyperkinesia, was localized almost exclusively to the oral region (P mean value of 0.01), whereas theL-Dopa hyperkinesia was more pronounced in the neck (P mean value of 0.05) and the extremities (P mean value of 0.05); (2) L-Dopa hyperkinesia showed an increasing tendency to oral preponderance with age, irrespective of the severity ofParkinsonism and extra-oral hyperkinesia, while tardive dyskinesia only itensified with age, without any change in distribution; and (3) extra-oral L-Dopa hyperkinesia was related to the localization and severity of pretreatment Parkinsonism, and more to bradykinesia than to rigidity and tremor. It is concluded that the irreversible neurotoxic effect of neuroleptic drugs may be associated with age-related changes in the oral somatotopic region of the basal ganglia (to be given consideration in any future search for the pathogenetic process underlying irreversible tardive dyskinesia), and that the pathophysiology of involuntary hyperkinesia in neuroleptic-treated psychiatric patients and in L-Dopatreated parkinson patients may consist of a primary dopamine deficiency (pharmacological or structural), and a secondary relative hyperactivity in the dopaminergic system ("dopaminergic hypersensitivity") possibly corresponding to hypoactivity in the cholinergic system.

Adult↗
PubMed1988

The effects of intravenous L-dopa on plasma renin activity, renal function, and blood pressure in man.

L-dopa 7 micrograms.kg-1.min-1 was given intravenously over 2 h to six healthy subjects, controlled by an infusion of saline on a separate occasion, with measurement of plasma renin activity (PRA), urinary sodium and potassium excretion, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), blood pressure, and pulse rate. Mean PRA fell by 50% following L-dopa, which was significantly different from the slight rise which occurred after saline infusion. There was a significant increase in urinary sodium excretion and effective renal plasma flow on infusion of L-dopa. Mean diastolic blood pressure fell during L-dopa infusion, in contrast to the slight increase which occurred during the control study. These observations confirm the anticipated renal dopaminergic effects of L-dopa and also suggest a dopaminergic influence on renin release in man.

Adult↗
PubMed1989

Inhibition of biopterin synthesis and DOPA production in PC-12 pheochromocytoma cells induced by 6-aminonicotinamide.

Pheochromocytoma cells (clone PC-12) were treated with 6-aminonicotinamide. Tetrahydrobiopterin content and DOPA production of the cells were determined by reverse-phase HPLC and subsequent electrochemical detection. The same chromatographic system was used to determine total biopterin (tetrahydrobiopterin, dihydrobiopterin and quinoide dihydrobiopterin) by fluorescence detection. Tetrahydrobiopterin plays a decisive role as cofactor of tyrosine hydroxylase for the biosynthesis of DOPA and dopamine. Addition of 6-aminonicotinamide to the culture medium resulted in the accumulation of 6-phosphogluconate, suggesting that PC-12 cells synthesize 6-aminonicotinamide-adenine-dinucleotide-phosphate (6-ANADP) by a glycohydrolase localized in the endoplasmic reticulum. This substance is known to be a strong inhibitor of 6-phosphogluconate dehydrogenase and leads to a blockade of the pentose phosphate pathway. In our experiments, the synthesis of biopterins was depressed after application of 6-aminonicotinamide. The decrease of intracellular tetrahydrobiopterin and total biopterin by 6-aminonicotinamide at different concentrations was strongly correlated with a reduced cellular DOPA production. The decreased content of biopterin cofactor was compensated by addition of the precursor sepiapterin, indicating that the NADPH2-dependent reductases in biopterin synthesis are not inhibited by the antimetabolite. However, DOPA production remained suppressed at the same time. After application of NADH2, we observed an increased DOPA production though the decreased biopterin levels remained almost unchanged. The results imply that the first step in the synthesis of biopterin from GTP as well as the recycling pathways of the oxidized cofactor might be the site of action of the antimetabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Aminonicotinamide↗
PubMed1977

Accumulation of dopamine in mouse pancreatic B-cells following injection of L-DOPA. Localization to secretory granules and inhibition of insulin secretion.

Accumulation and subcellular localization of dopamine (DA) in pancreatic B-cells and its effects on insulin secretion were investigated in mice following a single injection of L-3,4-dihydroxyphenylalanine (L-DOPA). Electron microscopic autoradiography showed that 3H-DA formed from administered 3H-DOPA was present over B-cells as well as over other types of islet cells. Pretreatment of the animals with a decarboxylase inhibitor greatly reduced the number of autoradiographic grains. In the B-cells the 3H-DA-grains were associated with the secretory granules. The location of the label may suggest an incorporation in the periphery of the beta-granule, rather than in the dense core, supposed to contain insulin. Accumulation of DA in the B-cells following L-DOPA administration was found to inhibit partially the insulin secretory response to different insulin secretagogues (glucose, glibenclamide and L-isopropylnoradrenaline (L-IPNA). Treatment with monoamine oxidase inhibitor + L-DOPA induced an almost total suppression of L-IPNA-stimulated insulin secretion, whereas glucose-induced insulin release was still only partially inhibited. Pretreatment with a decarboxylase inhibitor abolished the effects of L-DOPA. It is suggested that intracellularly accumulated DA in the B-cell exerts an inhibitory action on insulin releasing mechanisms induced by different secretagogues and that this action might involve interference with a calcium translocation process at the level of the secretory granule.

Animals↗
PubMed1976

Molecular biology of neurological and psychiatric disorders. I. Effect of parkinsonism, age, sex and L-dopa on platelet monoamine oxidase.

Since there is substantial evidence for a nigrostriatal dopamine defect in Parkinson's disease and since monoamine oxidase (MAO) appears to be essential for the degradation of dopamine, we investigated whether this enzyme is involved in the pathogenesis of this disease or in the therapeutic action of L-dopa. To gain a solid basis for our analysis we studied some properties of platelet MAO, at present the only practical in vivo source for human MAO. Substrate and inhibitor pattern clearly pointed to a predominant B-type character of this enzyme. By using 3 substrates, m-iodobenzylamine, p-methoxybenzylamine, and tyramine, we found a marked age and sex difference in MAO activity. In untreated parkinsonian patients, platelet MAO was slightly reduced as compared with age- and sex-matched controls. Treatment with L-dopa induced a further reduction of platelet MAO activity in both sexes, but more in men than in women. We conjecture that the action of L-dopa on parkisonian patients is twofold: L-dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity. Dopamine, formed from L-dopa, may thus have a better chance for survival in reaching the dopaminergic receptor. A new form of therapy, based on this concept, is proposed.

Adolescent↗
PubMed1975

Attempts to measure endogenous levels of dopa and 5-hydroxytryptophan in rat brain.

We have used previously published analytical methods of high sensitivity, developed in our laboratory, in an attempt to detect endogenous dopa and 5-hydroxytryptophan (5-HTP) in normal rat brain. In the brains of rats killed by decapitation we were unable to detect any dopa and found only a few ng/g of 5-HTP. Higher levels were found in the brains of rats killed by exposing their heads to microwaves. The levels of dopa found under these conditions varied considerably between different rat strains, and also between different experiments on the same strain, ranging between 2.5 and 13.8 ng/g. True resting levels may be lower than those observed because the procedure necessitated a short-lasting immobilization stress which increased the dopa (but not 5-HTP) levels. The 5-HTP levels were also variable and ranged between 5 and 25 ng/g. The highest levels of dopa and 5-HTP were found in the Japanese Wistar strain with spontaneous hypertension. Some analytical pitfalls are pointed out.

5-Hydroxytryptophan↗
PubMed1995

Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study.

We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.

Animals↗
PubMed1994

The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats.

In the present experiment we tested the effects of L-DOPA and amphetamine upon dopamine and DOPAC efflux in vitro from superfused corpus striatal tissue fragments of male rats who had been pretreated with reserpine. Male rats were treated with reserpine (5 mg/kg) or its vehicle at 24 hours prior to sacrifice and superfusion of the corpus striatum. Two different modes of L-DOPA (5 microM) and amphetamine (10 microM) stimulation, a brief 10-minute and a continuous 60-minute infusion, were tested for their ability to evoke striatal dopamine and DOPAC efflux. Depletion of monoamine storage capacity as achieved with reserpine significantly reduced the amount of basal dopamine and DOPAC released from superfused striatal tissue fragments of male rats. Although basal release rates were significantly reduced, the amount of dopamine and DOPAC released in response to in vitro L-DOPA infusions (10 or 60 minute infusions) was equivalent between reserpine and vehicle treated animals. In contrast, amphetamine stimulated DA release was significantly reduced in male rats treated with reserpine. For both L-DOPA and amphetamine, significantly greater amounts of dopamine were obtained with the 60- versus 10-minute infusion modes. These results demonstrate that the capacity for L-DOPA, but not amphetamine, to evoke dopamine efflux is unaltered under conditions when monoamine storage ability is diminished.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa.

A double-blind randomized crossover study of 0.125 mg Pergolide (Lilly) at bedtime versus 250mg L-Dopa + Carbidopa (Roche) was conducted in 16-day phases in 11 patients with idiopathic restless legs syndrome. Two patients reported a partial and 9 patients a complete relieve of motor restlessness while receiving Pergolide. Only 1 patient experienced an improvement of restlessness after L-Dopa. The patients showed polysomnographically a mean decrease in NMS cluster disturbed time by 45% from control on L-Dopa (p < 0.025) and by 79% from control on Pergolide (p < 0.001). In addition, Pergolide increased the total sleep time compared to L-Dopa (p < 0.05). In conclusion, the dopamine agonist Pergolide is superior to L-Dopa in the treatment of RLS and NMS.

Aged↗
PubMed1989

Intracerebral dialysis monitoring of striatal dopamine release and metabolism in response to L-dopa.

We have used intracerebral dialysis to monitor the striatal extracellular fluid (ECF) in rats with unilateral lesions of the nigrostriatal dopamine (DA) pathway. Dialysis samples were collected before and after L-dihydroxy-phenylalanine (L-DOPA) administration both in the presence and absence of carbidopa, an extracerebral DOPA decarboxylase (DDC) inhibitor. The baseline ECF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were always higher in the intact than in the lesioned striata. In the normal striata, dopamine (DA) concentrations increased following L-DOPA administration. Pretreatment with carbidopa prolonged the duration of the DA increase. In the lesioned striata, DA levels increased following L-DOPA administration only in animals pretreated with carbidopa. Following L-DOPA administration, striatal HVA and DOPAC levels increased considerably more in animals not pretreated with carbidopa than they did in pretreated animals. This increase was particularly marked in the lesioned striata and leads us to conclude that extracerebrally produced HVA and DOPAC can enter the brain extracellular space.

3,4-Dihydroxyphenylacetic Acid↗