SEARCH · Search PubMed
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.
The effects of three cumulative doses (20 mg/kg i.v.) of alpha-methyldopa were studied on pressor responses elicited by the stimulation of the central end of visceral or cutaneous afferences in the anaesthetized dog : vagus, superior laryngeal and saphenous nerves. As clonidine (previous results) alpha-methyldopa failed to modify these cardiovascular reflexes under our experimental conditions.
Immune hemolytic anemia and chronic active hepatitis developed concurrently in a 76-year-old man after prolonged therapy with methyldopa. Both complications disappeared following cessation of treatment with the offending drug and a short course of a high-dose corticosteroid (prednisone). Inhibition of T-suppressor lymphocyte function by methyldopa may be instrumental in the emergence of autoimmune complications following usage of the drug.
Based on previous studies with alpha-methyldopa (inhibitor of hepatic mixed-function monooxygenase system) and m-trifluoromethyl-alpha-ethylbenzhydrol, a new enzyme inducer Zixoryn, the authors studied the effect of the combined treatment of the two compounds on the hepatic drug-metabolizing enzyme activity in ten patients. There was no change in antipyrine half-life and its apparent volume of distribution (aVd) in the amount of D-glucaric acid excreted in the urine (indirect parameters of the mixed-function monooxygenase system's activity) after 1-week administration of 1000 mg alpha-methyldopa together with 300 mg Zixoryn per day. The two compounds counteracted each other's effects in the applied doses.
In a retrospective study of 82 patients with biliary carcinoma a higher than expected prevalence of methyldopa therapy was found. Carcinogenesis by electrophile reactive metabolites of methyldopa is discussed.
Two of four chimpanzees developed a moderately strong positive direct Coombs test after injection of stroma of their autologous erythrocytes that had been treated with alpha-methyldopa in the presence of diethyldithiocarbamate. Similar experiments with rabbits were unsuccessful. The results are concluded to be a demonstration that the first step in the development of autoantibody in alpha-methyldopa therapy is interaction of the oxidized drug with certain, as yet unidentified, peptides of the erythrocyte membrane.
A single-blind, prospective, crossover study of 27 ambulatory hypertensive outpatients was conducted to compare the antihypertensive effects of single daily dose versus multiple daily dose methyldopa regimens. Patients were randomly assigned to the two treatment modalities for a four-week study period. After four weeks patients were crossed over to the other study regimen. Each patient's blood pressure was determined three times daily, once each week. At the end of the study both treatment modalities were equally effective in controlling blood pressure levels. No serious adverse reactions were detected. This study has shown that patients currently on divided daily doses of methyldopa can be effectively treated on a single total dose of the medication.
An open crossover study was carried out in 10 Arab patients with mild to moderate hypertension to compare the effectiveness and tolerability of labetalol with alpha-methyldopa. Patients were started on either 100 mg labetalol or 250 mg alpha-methyldopa 3-times daily and, if necessary, the dosage adjusted by standard increments every 2 weeks over a period of a month until satisfactory control was achieved. This dosage was then maintained for a further 6 weeks before the patients were crossed over to the alternative treatment, similarly adjusted, after a wash-out period of 2 weeks on placebo. The results showed that both treatments produced effective blood pressure control and there was no significant difference in the maximum reduction achieved. The effect of the two drugs on heart rate was also similar. Both treatments were generally well-tolerated and side-effects were mild and similar with either drug.
The dopamine hypothesis of schizophrenia suggests that there is a functional excess of dopaminergic activity within the brain of schizophrenics. Alpha-methyldopa interferes with dopaminergic transmission in the central nervous system. We report a case of a schizophrenic in whom, after an overdose of alpha-methyldopa, there was a dramatic and apparently complete resolution of psychotic symptomatology, followed after a few weeks by a sudden return of psychosis.
A case of hepatitis induced by methyldopa and verified by means of challenge with the drugs is reported. The severe, chronic, aggressive inflammation greatly regressed after discontinuing the drug. The clinical differences, as well as those in laboratory findings disappeared. The electron-microscopic showed definite, but non-specific changes in the hepatic and sinusoidal mesenchymal cells. Our case was compared with the electromicroscopic picture of chronic aggressive hepatitis of unknown aetiology, and one essential difference was found in our hepatitis case as a result of methyldopa treatment: pathologic fibrogenesis did not occur. The rapid regression of the severe morphological picture can be attributed to this fact.
Methyldopa (400 micrograms/ml) abolished neurally evoked contractions of the guinea-pig vas deferens after 1.5 hr incubation. The tissue became supersensitive to noradrenaline and acetylcholine but was now insensitive to potassium chloride. On the other hand, tissues treated with 6-hydroxydopamine (6-OHDA) were supersensitive to noradrenaline but not to acetylcholine. The results suggest that cholinergic mechanisms may also be affected by methyldopa.
Alpha-methyldopa binds to human erythrocyte membrane proteins. A portion of this binding is readily dissociable in SDS but a significant amount is very tightly bound and does not come off even under rigorous conditions. The binding is increased under oxidizing conditions and very much inhibited in the presence of reducing agents as well as superoxide dismutase and catalase. Haemoglobin competes with membrane peptides for alpha-methyldopa binding. It is postulated that haemoglobin acts as a 'sink' for the drug in the intact cell and that the first step in the pathogenesis of Coombs positivity and haemolytic anaemia results from an alteration of a critical membrane peptide secondary to binding of the drug during normal membrane breakdown.
A patient with fatal submassive hepatic necrosis after methyldopa is described. Patient had positive L.E. cell preparation. The literature and the two previous cases of submassive hepatic necrosis were briefly reviewed. Methyldopa occasionally produces severe hepatitis, chronic active and rarely submassive necrosis.
A comparison of indoramin and methyldopa in the treatment of mild and moderate essential hypertension in 31 White middle-aged patients was made by means of a double-blind crossover trial. Equally satisfactory control of systolic and diastolic blood pressure, in the standing and supine positions, was achieved by both drugs. With a mean dose of 158 +/- 9 mg per day of indoramin the average fall in lying and standing blood pressures was 16/6 and 16/8 mmHg respectively. Equivalent values for methyldopa, with a mean dose of 1 540 +/- 90 mg per day, were 21/8 and 16/13 mmHg. Values for the two drugs are not significantly different. Also, there were no significant differences between the two drugs in their effect on the heart rate or in the incidence of side-effects.
Our objective was to evaluate the utility of an in vitro cell culture system (Caco-2) to study the pathways for the metabolism of L-alpha-methyldopa (MD) in the intestinal mucosa during its transepithelial transport. Caco-2 cell monolayers grown onto polycarbonate membranes in Transwells have been reported to exhibit morphological and biochemical properties similar to those of the human intestinal mucosa. After oral administration, MD has been reported to undergo extensive first-pass metabolism during its transport across the intestinal mucosa. In earlier studies, our laboratory showed that MD was rapidly transported across Caco-2 cell monolayers consistent with a carrier-mediated mechanism involving the large neutral amino acid transporter (Hu and Borchardt, 1990). Reversed-phase, ion-pair HPLC coupled to an electrochemical (amperometric) detector operating in the oxidative mode was used in this study to detect MD and its metabolites in the transport and cellular media. After rapid cellular uptake from the apical surface of Caco-2 cell monolayers, MD was predominantly metabolized to form MD-sulfate and MD-glucuronide and 3-O-methyl-methyldopa and its sulfated conjugate. Although methyldopamine was detected in minor quantities, it was present mainly as the sulfate and glucuronide conjugate. Although the cellular levels of MD and its metabolites rapidly reached steady-state, the corresponding basolateral levels continuously increased after an initial small lag-time. We observed that the 25-day-old Caco-2 cell monolayers used in this study were able to metabolize MD to a greater extent than those cultured for 11 days (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
In an open clinical trial, 30 compensated cardiac patients with essential hypertension were selected and randomly distributed. Treatment was given by means of two combinations of active agents, one containing 0.15 mg reserpine, 15 mg mefruside and 150 mg inositol nicotinate and the other 0.10 mg reserpine, 10 mg mefruside and 125 mg alpha-methyldopa. A randomized control group of 30 patients with essential hypertension received 0.15 mg reserpine, 15 mg mefruside and 150 mg isositol nicotinate exclusively over the same treatment period. By substituting only 125 mg alpha-methyldopa for 150 mg inositol nicotinate, the reserpine-mefruside portion can be reduced by one third while still obtaining the same antihypertensive effect.
A 74-year-old man developed an extensive erythematous skin eruption, fever, lymphadenopathy and eosinophilia probably due to methyldopa. The symptoms reappeared shortly after unintentional reexposure to the drug. The positive results of two in vitro tests for the detection of drug allergy not only give further support to the causal relationship between the drug and the symptoms, but also indicate the involvement of an immunologic, allergic mechanism. Although every individual symptom represented in our case has been reported in previous cases, the association of the symptoms together in one patient has never before been reported. An awareness that adverse reactions to methyldopa can mimic a variety of acute infectious diseases and lymphoproliferative disorders is the key to diagnosis and might prevent unnecessary hospitalizations, procedures, and use of potentially toxic antibiotics and chemotherapy.
MethylDOPA has the considerable (60-80%) and lasting RPE at both intraperitoneal (0.5-3.8 mmol/kg) and per os (3.8-7.1 mmol/kg) introduction in radiation dose 8 Gr (LD97/30). Optimal time for introduction is 0.5-3.0 hours intraperitoneally and 3-6 hours per os. Evidently, methylDOPA RPE is realized via alpha 2-adrenoceptors.
Systemic and regional hemodynamic changes were measured in five restained conscious rhesus monkeys before and after a 2-hour intravenous infusion of 50 mg/kg of alpha-methyldopa and, in another group of five monkeys, 5 to 10 mg injected into a lateral cerebral ventricle. Both routes of administration evoked similar degrees of hypotension, bradycardia and decreased cardiac output, although the cerebral intraventricular (i.c.v.) injections had more immediate and long-lasting effects. Both groups had a similar pattern of changes in the redistribution of cardiac output and blood flow that lasted at least 4 hours. Blood flow was maintained in the hepatic and renal arteries and decreased in skeletal muscle, heart, brain and skin. In contrast, i.c.v. injections of alpha-methyldopamine and alpha-methylnorepinephrine given at the same site evoked dose-related pressor responses that lasted up to 4 hours. The data suggest that alpha-methyldopa has important central action that inhibits sympathetic outflow, but that its hypotensive effect is either mediated only by endogenously formed metabolites or that its mechanism of action is not directly related to these metabolites at sites around the lateral and third cerebral ventricles in the monkey.