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At least 109 records · Page 6Linked to original sources
PubMed1998

L-DOPA exacerbates amphetamine-induced dopamine depletion.

Administration of L-DOPA to Parkinson patients has been suggested to exacerbate "functional denervation" of the nigrostriatal system. Therefore, experiments were conducted to determine if L-DOPA combined with the DOPA decarboxylase inhibitor, Ro4-4602 (benserazide hydrochloride) would potentiate amphetamine-induced neurotoxicity. Mice received two injections of saline or benserazide + L-DOPA (25.0 or 100.0 mg/kg) interspersed with four injections of amphetamine (15.0 mg/kg) at 2-h intervals. Significant depletion of striatal dopamine, DOPAC, and HVA was evident 1 wk following amphetamine administered with or without 25.0 mg/kg L-DOPA + benserazide, whereas 100.0 mg/kg L-DOPA + benserazide potentiated amphetamine-induced depletion of striatal dopamine (17 vs 28% of control values). This enhanced toxicity may be consequent to increased dopamine turnover following L-DOPA (360 vs 231%), a situation akin to that observed in compromised dopaminergic nigrostriatal systems of parkinsonian patients. Furthermore, striatal 5-HT was not altered by amphetamine alone, whereas concurrent administration of L-DOPA/ benserazide depleted 5-HT to 82% of control values. No changes were evident in the frontal cortex following amphetamine with or without concurrent L-DOPA/benserazide; however, L-DOPA/benserazide administered alone reduced 5-HT and 5-HT turnover to 58% of control values.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Intravenous L-5-hydroxytryptophan in normal subjects: an interdisciplinary precursor loading study. Part III: Neuroendocrinological and biochemical changes.

In a precursor study with i.v. 1-5HTP (Ro 3-5940) after peripheral decarboxylase inhibition with benserazide (Ro 4-4602) in healthy human subjects the following biochemical changes were found: 1. Prolactin release was stimulated by benserazide alone, and further stimulated by 1-5HTP (more in women than in men). 2. Basal growth hormone secretion was not affected by benserazide, but was significantly stimulated by 1-5HTP, often to extremely high values. The time course of growth hormone release followed that of mood elevation in 8/11 subjects (and was even correlated in 3), providing data for speculation as to the interrelationships between affective state and neuroendocrinological function. 3. Cortisol levels were higher than normal throughout the experiment, but followed the diurnal decline. A late stimulation of cortisol release after 1-5HTP was observed. 4. The lack of increased platelet serotonin after 1-5HTP indicated efficacious peripheral decarboxylase inhibition by benserazide. 5. Benserazide treatment inhibited platelet MAO activity in certain subjects. Short-term increases in MAO activity after 1-5HTP were observed. 6. 1-5HTP displaced albumin-bound tryptophan by 20%.

5-Hydroxytryptophan↗
PubMed1982

Prolactin response to acute administration of different L-dopa plus decarboxylase inhibitors in Parkinson's disease.

Plasma prolactin (PRL) levels modifications after acute administration of L-dopa, L-dopa plus carbidopa and L-dopa plus benserazide were studied in parkinsonian patients. PRL increase after benserazide was compared with PRL response after carbidopa at the same dosage in untreated parkinsonian patients. A further study of the hyperprolactinemic effect of benserazide was performed in vitro on isolated and dispersed rat pituitary cells. The data gathered indicate that benserazide-induced hyperprolactinemia in parkinsonian patients could be due to a direct effect of the drug at the hypothalamic level and consequently to an inhibition of dopamine decarboxylation in the tuberoinfundibular dopaminergic system. It is not possible to exclude, however, that benserazide could exert its biological activity through the production of active metabolites in vivo.

Aged↗
PubMed1996

In vivo microdialysis to determine the relative pharmacokinetics of drugs.

The purpose of this study was to evaluate a simultaneous microdialysis method in blood and brain striatum to determine the relative pharmacokinetics and metabolism of L-3,4-dihydroxypenylalanine (L-dopa). L-Dopa (250 mumol/kg) was administered to rats with or without the aromatic amino acid decarboxylase (AADC) inhibitor carbidopa (25 mumol/kg) or benserazide (25 or 62.5 mumol/kg). L-Dopa, its metabolites, and AADC inhibitors in dialysates were analyzed by high performance liquid chromatography with an electrochemical detector. A moment analysis was also made to obtain pharmacokinetic parameters. After administration of L-dopa alone, it and its related metabolites were detected in both dialysates of blood and brain striatum. Coadministration of carbidopa (25 mumol/kg) or benserazide (62.5 mumol/kg) significantly enhanced the striatal amount of L-dopa by 8.0 and 6.1 times, respectively. Carbidopa and benserazide also increased striatal amounts of L-dopa metabolites, such as 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol. Inhibition effect of benserazide on an extracerebral decarboxylation of L-dopa to dopamine (DA) was stronger than that of carbidopa. Carbidopa showed a higher striatal level of DA than benserazide. These results suggest a different effect of the two inhibitors on the DA formations in blood and brain striatum, and on the L-dopa transport through the blood-brain barrier (BBB). Thus, microdialysis is an easy and available method for simultaneously assessing the in vivo relative pharmacokinetics and metabolism of drugs in systemic circulation and a target organ.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Pituitary hormone secretion after inhibition of L-aromatic amino acid decarboxylase activity in man.

The effect of acute administration of 200 mg benserazide, an L-aromatic amino acid decarboxylase inhibitor, on pituitary hormone secretion in humans was studied. Benserazide induced in all subjects a quick and marked increment of serum prolactin (Prl) and TSH levels: at 180 min TSH and Prl levels were still significantly higher than the baseline values. Women with normal menstrual cycles showed a Prl response to benserazide which was significantly greater than that observed in post-menopausal women and men. In another experiment six normal men received 10 mg of domperidone, a peripheral dopamine receptor blocker. The hormonal changes induced by domperidone were comparable to those obtained with benserazide. Since domperidone and benserazide are thought not to cross the blood-brain barrier, these results suggest that dopamine regulates Prl and TSH secretion through extra blood-brain barrier structures.

Adult↗
PubMed1993

Involvement of renal dopamine synthesis in the diuretic effect of furosemide in normohydrated rats.

The present study was designed to investigate whether the modification of dopamine synthesis affects furosemide responses. Experiments were performed on pentobarbital-anesthetized rats. Basal urine flow was approximately 3 microliters/min-1/g-1 of kidney weight (k.w.); furosemide (0.2 mg/kg-1 i.v.) induced a rapid diuretic effect (19.3 +/- 1.4 microliters/min-1/g-1 of k.w.). The dopadecarboxilase inhibitor, benserazide (25 mg/kg-1 i.v.), reduced furosemide-induced diuresis to 8.3 +/- 2.1 microliters/min-1/g-1 of k.w., whereas levo-dihydroxyphenylalanine (L-dopa; 1 micrograms/kg-1/min-1 infused for 60 min) increased it to 41.4 +/- 6.1 microliters/min-1/g-1 of k.w. Natriuretic response and fractional Na+ excretion induced by furosemide were significantly lower in benserazide-treated and higher in L-dopa-treated animals. Urine dopamine (DA) excretion was enhanced by furosemide from 0.44 +/- 0.05 to 0.98 +/- 0.22 ng/min-1/g-1 of k.w. and was markedly reduced in benserazide-pretreated animals, whereas both basal DA excretion and that induced by furosemide were increased significantly during L-dopa infusion. However, in benserazide- or L-dopa-treated animals, basal urine flow was not different from the control group. Urine furosemide excretion was reduced by 60% by benserazide treatment and increased by 62% during L-dopa infusion. The results are consistent with the suggestion that although endogenous DA is apparently unimportant in the maintenance of basal urine output, it is involved in furosemide-induced diuresis. The diuretic response can be altered by acute administration of substances that affect dopamine synthesis.

Animals↗
PubMed1975

The effect of L-dopa on young patients with simple schizophrenia, treated with neuroleptic drugs: a double-blind cross-over trial with Madopar and placebo.

Thirteen out of 18 young out-patients with simple schizophrenia under neuroleptic treatment completed a double-blind cross-over trial with Madopar [L-Dopa + benserazid (a peripheral decarboxylase inhibitor)] and placebo. Nine patients were given 900 mg L-Dopa + 225 mg benserazid daily, 1 patient received 600 mg L-Dopa + 150 mg benserazid, and 3 patients, 300 mg L-Dopa + 75 mg benserazid. In these doses, L-Dopa was effective against emotional withdrawal, blunted affect, tendency to isolation and apathy, without inducing or aggravating productive, accessory symptoms. The activity score, according to the specific activity-withdrawal scale, was significantly increased (P less than 0.05), whereas the total BPRS score (Brief Psychiatric Rating Scale) was slightly, but significantly reduced (P less than 0.05). In cases where L-Dopa had to be limited to 600 and 300 mg daily, a tendency to anxiety, distortion of thinking, and a sense of unreality were observed, depending on the dose of L-Dopa. In no case were gastrointestinal, cardiovascular or neurological side-effects observed.

Adult↗