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At least 325 records · Page 18Linked to original sources
PubMed1997

Pretreatment with quinpirole inhibits the central antihypertensive effects of rilmenidine and alpha-methyldopa in conscious rats.

Treatment of conscious spontaneously hypertensive rats (SHR) with the dopamine D2 receptor agonist quinpirole causes a short-lasting pressor response and apparent desensitisation to the effects of subsequent injections of quinpirole or central antihypertensives such as clonidine. In the present study, a number of aspects of this apparent desensitisation were investigated. Thirty minutes after intravenous injection of quinpirole into spontaneously hypertensive rats, treatment with the dopamine D2 receptors antagonist raclopride caused a significant fall in blood pressure. At this time point, circulating levels of vasopressin were not significantly different compared to controls. In Brattleboro rats, the pressor response to quinpirole was reduced in the first 15 min after injection, but not difference in blood pressure was observed at later time points. In SHR which had been treated with quinpirole, the central antihypertensive effects of rilmenidine or alpha-methyldopa were significantly inhibited. By contrast, the bradycardia induced by these drugs was similar in quinpirole-treated rats and controls. Quinpirole pretreatment caused an enhancement of the hypotension but a reduction of the reflex tachycardia after intravenous treatment with hydralazine. In SHR treated with methylatropine and quinpirole, the upper plateau of the sympathetic baroreceptor-heart rate reflex curve was reduced. These results show that treatment with quinpirole has marked effects on central sympathetic vasomotor mechanisms which are the target of antihypertensive drugs such as rilmenidine and alpha-methyldopa. At least some of these effects may occur at the level of the sympathetic baroreflex. Moreover, while the effects of quinpirole on sympathetic regulation are prolonged, the initial pressor response is counteracted by an as yet unidentified compensatory mechanism which can be unmasked when quinpirole is displaced from its receptor by dopamine D2 receptor antagonist treatment.

Animals↗
PubMed1991

Stability-indicating high-performance liquid chromatographic assay for alpha-methyldopa in sustained-release capsules.

A stability-indicating high-performance liquid chromatographic assay has been developed for the analysis of alpha-methyldopa (MD) in sustained-release capsules and in the presence of MD decomposition products and an MD industrial impurity, 3-O-methyl-methyldopa (MMD). The method utilizes reversed-phase chromatography (cyano-bonded column), an acidic mobile phase containing sodium heptanesulphonate as ion-pairing reagent and UV detection. Detector responses were linear in the ranges 0.5-200 microgram/ml for MD and 0.2-100 microgram/ml for MMD. The mean recoveries of MD from authentic sample and sustained-release capsules were 100.09 +/- 0.38 and 100.38 +/- 0.46%, respectively. The recovery of MD added to degraded MD, were 99.69% by the proposed method and 153.13% by the US Pharmacopeial (USP) spectrophotometric method. The method is sensitive, accurate and rapid and can be used in routine analysis for MD.

Capsules↗
PubMed1984

Sensitive high-performance liquid chromatographic assay using electrochemical detection for a novel prodrug ester of methyldopa, pivaloyloxyethyl 3-(3,4-dihydroxyphenyl)-2-methylalaninate, in plasma and urine.

The pivaloyloxyethyl ester of methyldopa is an antihypertensive prodrug possessing improved bioavailability properties over methyldopa. A sensitive cation-exchange, high-performance liquid chromatographic assay using electrochemical detection has been developed for the ester in plasma and urine in order to determine the extent of its hydrolysis after oral administration. The chromatographic conditions involve two Altex Partisil 10 SCX columns (25 cm X 4.6 mm) in series; a mobile phase consisting of methanol, potassium phosphate buffer, pH 3.0, and EDTA disodium dihydrate; and an electrochemical detector set at 0.5 V. The pivaloyloxyethyl ester in plasma or urine is extracted into ethyl acetate, back-extracted into 0.1 M sulfuric acid, and analyzed directly by high-performance liquid chromatography. For urine, the ethyl acetate extract is washed with a buffer (pH 8.0) prior to the back-extraction step. The assay gives a linear response over the concentration range of 10-160 ng/ml in plasma and 20-400 ng/ml in urine.

Animals↗
PubMed1983

The effect of chronic alpha-methyldopa upon sexual function in the adult male rat.

Erectile impotence is a commonly reported undesired side effect in patients treated for hypertension with alpha-methyldopa. However, the mechanism of that dysfunction has not been determined. In this study we report the effect of 12 days of daily intraperitoneal injections, 300 mg./kg., of alpha-methyldopa on adult male, Long-Evans rats and their age-matched saline controls. The effect of the drug upon copulation, penile reflexes and tissue catecholamines was measured. The results showed significant differences between control and experimental animals in all parameters studied. Tests of copulatory ability showed significant decreases in mounts from 5.8 +/- 1.6 (mean +/- standard error) to 3.1 +/- 1.3; penile intromissions from 27.0 +/- 3.8 to 4.8 +/- 1.9; and ejaculations from 2.1 +/- 0.3 to 1.1 +/- 0.6 per 30 minute test period. Penile reflexes measured as erection and cup formation showed similar significant reductions. The norepinephrine content of the penile corpora in the controls was 0.460 +/- 0.084 ng./mg. wet weight and 0.112 +/- 0.022 ng./mg. wet weight in the experimental group. There were similar significant reductions of norepinephrine content in the vas deferens of these animals 32.95 +/- 4.31 ng./mg. and 0.25 +/- 0.1 ng./mg. wet weight in the control and experimental groups respectively.

Animals↗
PubMedDate not supplied

Effect of therapeutic levels of magnesium sulphate, methyldopa, hydralazine and phenobarbitone on normal term human trophoblast in vitro.

The development of a technique allowing prolonged culture in vitro of normal term human trophoblast facilitates examining what effects, if any, drugs commonly used in pregnancy may have on placental tissue. Dosages compatible with therapeutic blood levels of magnesium sulphate, methyldopa, hydralazine and phenobarbitone were tested individually in vitro on monolayer cultures of normal term trophoblast. Hydralazine and magnesium sulphate additions resulted in a 100 per cent loss of viability of trophoblast cells. Phenobarbitone caused an 8 per cent decrease in cell viability, while methyldopa caused only a 2 per cent decrease in cell viability.

Female↗
PubMed1988

Congestive heart failure and respiratory arrest secondary to methyldopa-induced hemolytic anemia.

We report a case of methyldopa-induced hemolytic anemia in a 64-year-old woman who presented to the emergency department in congestive heart and respiratory failure. She subsequently suffered a respiratory arrest and required endotracheal intubation and brief CPR. After the initial evaluation revealed anemia and a 3+ positive Coombs' test, a diagnosis of methyldopa-induced hemolytic anemia was entertained. Withdrawal of the drug and supportive therapy resulted in the complete recovery of the patient. Emergency physicians should be aware of this syndrome and be able to diagnose it early in its course, avoiding potential morbidity and mortality. A discussion of the pathophysiology, diagnosis, treatment, and prognosis of the syndrome is given.

Anemia, Hemolytic↗
PubMed2002

Quantification of methyldopa in human plasma by high-performance liquid chromatography-electrospray tandem mass spectrometry application to a bioequivalence study.

A method based on LC-MS-MS is described for the determination of methyldopa in human plasma using dopa-phenyl-D3 as the internal standard. The method has a chromatographic run time of 5.5 min and was linear in the range of 20-5000 ng/ml. The limit of quantitation was 20 ng/ml, the intra-day precisions were 7.3, 5.4 and 4.3% and the intra-day accuracies were -8.0, -1.3 and -2.0% for 30, 600 and 3000 ng/ml, respectively. The inter-day precisions were 7.7, 0.5 and 0.7% and the inter-day accuracies were 0.2, -1.1 and -2.3%, respectively, for the above concentrations. This method was employed in a bioequivalence study of two tablet formulations of methyldopa.

Calibration↗
PubMed1981

Effects of labetalol and methyldopa on renal function.

Renal function studies were performed in subjects with mild hypertension treated with labetalol (n = 5) and moderate to moderately severe hypertension treated in a random double-blind fashion with either labetalol (n = 6) or methyldopa (n = 6). Drugs were given in doses sufficient to reduce standing diastolic blood pressure to less than 90 mm Hg. This was achieved in all subjects without significant side effects. Inulin clearance, para-aminohippurate clearance, filtration fraction, free-water clearance, and maximal concentrating ability was assessed before and after 15 days of drug. No alterations in any parameter were noted with labetalol. Inulin clearance fell by 13% (p less than 0.05), and filtration fraction fell from 0.23 to 0.18 (p less than 0.02), but other parameters of renal function did not change with methyldopa.

Adult↗
PubMed1990

Effect of pH on the oxidation pathway of alpha-methyldopa catalysed by tyrosinase.

This paper deals with the quantitative description of the effect of pH on the oxidation pathway of alpha-methyldopa. Tyrosinase catalyses the oxidation by molecular oxygen of alpha-methyldopa to o-alpha-methyldopaquinone, which evolves non-enzymically through a branched pathway with cyclization or hydroxylation reactions. The intermediates of the hydroxylation branch have been identified, and the corresponding rate constants have been determined. These compounds, which have been detected in melanosomes and in tumour cells, have great cytotoxic power and could have physiological significance in acidic media.

Basidiomycota↗
PubMed1976

Reduction of the hypotensive effect of clonidine and alpha-methyldopa by various psychotropic drugs.

1. In chloralose-anaesthetized cats the centrally induced hypotensive effect of clonidine, and in some cases alpha-methyldopa, was diminished by pretreatment with a variety of tricyclic antidepressants and neuroleptic agents. 2. The interaction is assumed to occur at the central alpha-adrenoreceptors. Clonidine or alpha-methyl-noradrenaline (from alpha-methyldopa) are the agonists, and the aforementioned psychotropic drugs are the antagonists. 3. Psychotropic drugs which are not alpha-receptor blockers, like butyrophenone neuroleptics (pimozide and haloperidol) or benzodiazepine tranquillizers, do not significantly diminsh the centrally induced hypotensive effect of clonidine.

Animals↗
PubMed1976

Interaction of dopamine, methyldopa and reserpine in the sympatho-adrenal system in essential hypertension.

1. The interactions of dopamine, reserpine and methyldopa on blood pressure of normal subjects and of those with essential hypertension were examined. 2. When biosynthesis of noradrenaline from dopamine was blocked by reserpine, dopamine induced a prominent depressor effect in essential hypertension. 3. The long-term treatment with methyldopa induced a marked potentiateion of the pressor action of domapine in hypertension, although no significant pressor response was found in normal subjects. 4. It is suggested that methylnoradrenaline may accumulate in peripheral nerve endings of patients with essential hypertension in comparison with normal subjects, and this accumulated methylnoradrenaline potentiates the pressor response to dopamine in essential hypertension.

Adult↗
PubMed1976

A within-patient comparison of bethanidine, methyldopa and propranolol in the treatment of hypertension.

1. A within-patient comparison showed that bethanidine, methyldopa and propranolol produced similar control of the blood pressure. 2. Unlike bethanidine, propranolol did not produce postural and exercise hypotension; methyldopa was intermediate in effect. 3. Overall side effects were of a similar incidence though there were differences in incidence of particular side effects.

Bethanidine↗
PubMed1977

Effect of alpha-methyldopa on the pulmonary vascular changes induced by chronic hypoxia in rats.

1. Groups of young rats were kept in a hypoxic chamber or in air as control animals for 28 days. 2. Hypoxic and control animals were treated with either alpha-methyl-3,4-dihydroxyphenylalanine (alpha-methyldopa) or distilled water. 3. alpha-Methyldopa significantly reduced the increase in pulmonary artery pressure and right ventricular hypertrophy induced by chronic hypoxia and partially prevented the histological changes in the small pulmonary vessels.

Animals↗
PubMed1979

Effect of exercise in hypertension controlled with metoprolol or methyldopa.

1. The adequacy of the control of essential hypertension during exercise was studied in patients whose resting blood pressure had been controlled for 1 year with either metoprolol or methyldopa. 2. Systolic blood pressure increased with exercise in both groups, the increase being significantly less in the metoprolol group than in the methyldopa group.

Adult↗
PubMedDate not supplied

Clinical and serologic management of patients with methyldopa-induced positive antiglobulin tests.

Methyldopa can produce both a positive direct antiglobulin test and less commonly a positive indirect antiglobulin test. When the drug-induced antibody is present in the serum, it acts as a panagglutinin and reacts with all normal red blood cells; consequently crossmatch-compatible blood cannot be prepared. Although the methyldopa-induced antibody itself rarely produces hemolysis, difficulties can arise in previously unscreened patients in whom the panagglutinin may mask an unknown, pre-existing, and potentially hemolytic alloantibody. We report on our clinical and serologic management of 14 such patients for whom transfusions were requested.

Antibody Formation↗
PubMed2000

Influence of Avicel PH-301 on the compressibility of alpha-methyldopa and phenobarbitone in direct compression.

The aim of this work was to investigate the compressibility behavior of alpha-methyldopa and phenobarbitone using a Korsch EK0 instrumented eccentric tablet machine, with force-time and force-displacement curves constructed and applied to calculate different compressional values to study the compressional behavior. The results of this work revealed a difference in compressibility behavior between the two drugs during the compressional process. alpha-Methyldopa gave an abnormal compressional curve with high friction in the pre- and postcompressional phases. A residual force could be seen on the lower punch. Furthermore, capping and sticking were observed visually during tablet pressing, indicating poor compressibility behavior. In the case of phenobarbitone, no friction was observed in the precompressional phase, but there was higher friction in the postcompressional phase, especially in the ejection phase. The compressibility of the drugs was improved by the addition of Avicel PH-301 and magnesium stearate.

Anticonvulsants↗
PubMed1986

Molecular localization, developmental expression and nucleotide sequence of the alpha-methyldopa hypersensitive gene of Drosophila.

The region surrounding the dopa decarboxylase gene of Drosophila contains a cluster of functionally related genes, many of which affect cuticle development and/or catecholamine metabolism. In this report we describe the molecular mapping and sequencing of a full-length cDNA copy of a transcript that maps to the alpha-methyldopa hypersensitive region. Developmental RNA blots show stage-specific patterns of transcription and multiple RNA transcripts. A 2-kb transcript is most abundant at about 12 hr of embryogenesis, and lower levels are detected throughout most of embryogenesis. Lower levels of this transcript are also detected in adults. Smaller stage-specific transcripts are detected in late third-instar larvae. This pattern of transcription is consistent with the known lethal phases and phenotypes of the alpha-methyldopa hypersensitive gene (amd). Based on map position, pattern of transcription, homology with dopa decarboxylase and association with altered DNA in mutants, we conclude that this transcript represents the amd gene.

Amino Acid Sequence↗
PubMedDate not supplied

Fatal methyldopa-associated granulomatous hepatitis and myocarditis.

A 78-year-old woman developed spiking fever of obscure etiology while receiving long term therapy with methyldopa and died suddenly seven days after admission to the hospital. Autopsy showed widespread granulomas in the liver, spleen, lymph nodes and bone marrow, interstitial myocarditis with granulomatous features and renovascular vasculitis. Eosinophils were prominent in the granulomas and in the myocardium consistent with a drug-induced cell mediated hypersensitivity reaction presumably triggered by methyldopa. The need for a careful drug history in fever of obscure etiology is emphasized.

Aged↗