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PubMed1985

Effect of alpha-methyldopa excreted in human milk on the breast-fed infant.

A nursing infant whose mother took alpha-methyldopa (alpha-MD) was followed for 3 months. Analysis of maternal serum and milk as well as the infant's serum and urine for alpha-MD revealed that the drug was excreted into maternal milk, absorbed by the infant and excreted in her urine, but no adverse clinical effects were noted during the follow-up period. alpha-MD is excreted in human milk in concentrations that probably do not harm the breast-fed infant.

Adult↗
PubMed1985

[Effect of alpha-methyldopa (Dopegyt) on blood pressure in hypertensive pregnant patients].

Forty-three patients hospitalised for chronic hypertension or superimposed toxemia in late pregnancy were treated with Dopegyt-orally in constant dosage. Blood pressure dropped at the beginning of therapy. In the further course of treatment blood pressure re-increased in 14 patients, that other antihypertensive drugs had to be administered additionally. alpha-methyldopa alone is sufficient only in a part of the hypertensive patients.

Adult↗
PubMed1979

Antihypertensive effect of prazosin in combination with methyldopa, clonidine, or propranolol.

Seventeen hypertensive out-patients, more or less unresponsive to previous treatment with antihypertensive drugs, were treated in a cross-over fashion with placebo, prazosin (Pz), methyldopa (MD), Pz + MD, Pz + clonidine (C) and Pz + propranolol. The antihypertensive responses to Pz 2 mg t.i.d. and MD 250 mg t.i.d. were poor, and only modest when the drugs were combined. The combination of Pz with low doses of C was about as effective as Pz + MD, and some patients failed to respond to it. Nor was the combination of Pz + propranolol effective in those cases but the addition of a diuretic produced good responses in all patients. Side effects were few. It is concluded that a combination of central and peripheral sympathetic blockade does not necessarily produce normotension, and that a diuretic added to this combination greatly improves the response.

Adult↗
PubMed1983

[Antinuclear antibodies and lupus induced during treatment of arterial hypertension. Role of beta-blockers and alpha-methyldopa].

Comparison of hypertensive patients receiving no treatment with subjects of the same age reveals the presence of antinuclear antibodies in twice as many of the former as the latter. Various antihypertensive drugs increase this prevalence. They may induce iatrogenic lupus. Alpha-methyldopa: the frequency of antinuclear bodies is three times greater than in untreated hypertensive patients. However there are no reported cases of clinical symptomatology of induced lupus. Beta-blockers. Practolol, acebutolol, labetalol, atenolol, timolol, metoprolol, pindolol and oxprenolol are suspected of increasing antinuclear antibodies. These drugs may be weak inducers of iatrogenic lupus when compared with major drugs: procainamide, high doses of hydralazine and D-penicillamine.

Adrenergic beta-Antagonists↗
PubMed1981

Long-term treatment of hypertensive with methyldopa. VI. Patient with target organ disease.

In a study conducted retrospectively, the incidence of new hypertension-associated complications was low during administration of methyldopa as part of a total antihypertensive regimen in 435 patients with essential hypertension. Antihypertensive therapy was not associated with further morbid events among patients with a pretreatment history of myocardial infarction or stroke.

Adolescent↗
PubMed1981

Long-term treatment of hypertension with methyldopa. VIII. Overview.

A multiclinic retrospective study in patients who received methyldopa, some for up to 10 years, has provided a large body of long-term data on the efficacy and tolerability of the drug as part of an antihypertensive regimen. Blood pressure and dosage data were analyzed over the first 4.5 years. The results of this survey are summarized here.

Adolescent↗
PubMed1984

The effect of single-dose methyldopa and diuretic on BP and left ventricular mass.

The effect of a single daily dose of 500 mg of methyldopa with 50 mg of hydrochlorothiazide and 5 mg of amiloride hydrochloride was studied in 21 patients with mild to moderate hypertension. It was shown that the average morning BP changed from 182/103 +/- 15/9 mm Hg to 145/83 +/- 16/8 mm Hg following one day of treatment. Similarly, the average of seven hourly measurements (7BP) dropped from 170/99 +/- 11/7 mm Hg to 145/86 +/- 11/8 mm Hg. In 12 patients, the same therapy lowered the morning BP from 186/104 +/- 16/9 mm Hg to 144/83 +/- 15/8 mm Hg and the 7BP from 168/98 +/- 10/6 mm Hg to 142/83 +/- 12/7 mm Hg following three weeks. After eight weeks, normal values were still maintained. Left ventricular mass was elevated in all the patients (330 +/- 67) and dropped by an average of 12% and 17% by three and eight weeks after initiation of therapy. Unchanged left ventricular end diastolic volume and decreased muscle thickness indicate true reduction in hypertrophy in addition to the BP-lowering effect of this combined single-dose therapy described.

Adult↗
PubMed1980

alpha-methyldopa reduces locomotor activity in rats via its metabolite, alpha-methylnorepinephrine, acting on alpha 2-adrenoceptors.

The decrease in locomotor activity in rats caused by alpha-methyldopa (alpha-MD), 400 mg/kg p.o. was antagonized by treatment with yohimbine, a selective antagonist of alpha 2-adrenoceptors. Effective doses of yohimbine ranged from 0.25--2.0 mg/kg s.c., whereas yohimbine at 0.125 mg/kg did not significantly affect the decrease in locomotor activity caused by alpha-MD. Similar results were obtained in studies on the interaction between clonidine injected intracisternally and various doses of yohimbine given s.c., except that the higher doses of yohimbine completely blocked the depression of locomotor activity caused by clonidine, but not by alpha-MD. The depression of motor activity following alpha-MD was not offset by prazosin, a preferential alpha 1-antagonist. At the same doses that failed to alter the action of alpha-MD, prazosin was effective in antagonizing the increase in motor activity resulting from intracisternally injected methoxamine, a selective agonist, at alpha 1-receptors. Treatment with FLA-63, using a regimen that was shown to inhibit dopamine-beta-hydroxylase in brain, caused a diminution in the ability of alpha-MD to depress locomotor activity. These findings indicate that alpha-MD reduces locomotor activity in the rat at least in part via the formation of alpha-methylnorepinephrine which acts on alpha 2-adrenoceptors.

Animals↗
PubMed1984

In vivo mutagenic effect of methyldopa. 1. Dominant lethal test in male mice.

The dominant lethal test was used to evaluate the mutagenic potential of methyldopa, an antihypertensive drug, in male mice. In the series treated, animals were exposed to 480 or 960 mg/kg of the drug as a suspension in 1% gum acacia via the oral route. A separate group of males served as control. Following treatment each male of the control, as as well as the treated series, was mated to two untreated virgin females each week for a period of 6 consecutive weeks. All mated females were sacrificed on the 10th day of separation and their ovaries and uterine contents were examined. Corpora lutea, implantations and resorptions were recorded. The drug treatment did not impair the mating capacity and fertility. Pre- and post-implantation losses were assessed. Higher incidences of post-implantation losses and abortion, and lower incidences of total implantations particularly at higher dose levels clearly reveal a dominant lethal effect of the drug.

Abortion, Spontaneous↗
PubMedDate not supplied

Circulatory changes during and after surgical anesthesia in hypertensive patients treated with clonidine, methyldopa and reserpine.

The cardiovascular changes in 27 hypertensive patients belonging to WHO classes I-II and treated with either clonidine, methyldopa or reserpine during thiopentone-N2O-O2-relaxant-analgesic anesthesia were studied. The variations in systolic and diastolic blood pressure and heart rate during induction of anesthesia and surgery did not differ according to the antihypertensive drug with which the patient was treated. Hypokalemia was found to be the most common postoperative complication in all study groups. The results suggest that the selection of antihypertensive drug does not form a risk factor when hypertensive patients are being prepared for anesthesia and surgery.

Adult↗
PubMed1982

[Alpha-methyldopa and brain monoamines].

Alpha-methyldopa (alpha-MDP) is a widely used hypotensive agent, and it is considered to act on the central nervous system. In the present study, 6-hydroxydopa (6-OHDP) was injected into spontaneously hypertensive rats in a dose of 50 mg/kg on the 19th and 21st days of gestation. Dopamine contents were not changed, but norepinephrine (NE) decreased at 12 weeks of age. When the effect of alpha-MDP was examined at the age of 30 to 40 weeks, the decrease in blood pressure induced by 300 mg/kg alpha-MDP i.p. was significantly attenuated in the 6-OHDP treated rats. Whenever the hypotensive effects of alpha-MDP were inhibited, production of alpha-methylnorepinephrine (alpha-MNE) was markedly reduced only in the spinal cord. 6-Hydroxydopamine (6-OHDA) was also injected into the spinal cord at the C4 level. Although alpha-MDP lowered blood pressure in both 6-OHDA treated and non-treated control rats, the decreased in 6-OHDA treated rats tended to be less pronounced. The accumulation of alpha-MNE in the caudal area of the spinal cord was markedly reduced. Furthermore, in order to destroy the spinal serotonergic neurons selectively, we used intraspinal 5,7-dihydroxytryptamine (5,7-DHT) in the same manner as 6-OHDA injection. In 5,7-DHT treated rats, the blood pressure was decreased fully. These observations seem sufficient to hypothesize, although not to conclude, that the effect of alpha-MDP on the blood pressure is dependent at least partly on the biotransformation to alpha-MNE in the spinal noradrenergic neurons.

Animals↗
PubMed1983

Toxicity of methyldopa (Aldomet) to mouse neuroblastoma cells in vivo.

The adrenergic blocking agent methyldopa (Aldomet) is toxic to C-1300 neuroblastoma cells in vivo. Four injections of Aldomet at a dose of 7.5 mg/injection were given over a period of 24 hr to C-1300 neuroblastoma-bearing mice. This treatment killed a significant proportion of the C-1300 neuroblastoma cells. Flow cytometric data suggest that sensitivity of tumor cells to Aldomet is not related to the cell cycle.

Animals↗
PubMed1981

[Guanfacine versus alpha-methyldopa in benign essential hypertension. An ambulatory group study].

Alpha-methyldopa and guanfacine, both of which are predominantly centrally acting antihypertensives, were compared in a double-blind randomized trial involving seven practising physicians and a total of 78 patients. The whole trial lasted one year, with individual treatment periods of between 5 and 14 weeks. The reduction achieved in mean systolic and also diastolic blood pressure did not differ significantly between the two groups; nor was there any significant difference in responder or nonresponder rates. Blood pressure was normalized in approximately 80% of the patients in both groups. The incidence of side effects was kept down by starting treatment with a low dose and increasing it gradually. The average dose at the end of the trial was 2.6 mg daily for the guanfacine patients and 750 mg daily for those given alphamethyldopa.

Adolescent↗
PubMed1982

Methyldopa in the elderly hypertensive.

The on-going study by the European Working Party on High Blood Pressure in the Elderly (EWPHE) is described and the results in patients receiving either placebo or active treatment (hydrochlorothiazide plus triamterene, with the addition of methyldopa if necessary) are discussed. Over the 5-year period assessed, there has been a reduction in sitting blood pressure in both groups, but to a significantly greater extent in those receiving active treatment. No statistically significant differences in morbidity and mortality between the groups has been noted and there have been very few reports of side-effects or intolerance.

Aged↗
PubMed1980

Penbutolol: comparison of its antihypertensive effect with that of alpha-methyldopa in patients with primary hypertension.

The antihypertensive effect of 80 mg/day of the newly synthesized beta-blocker 1-tert. butylamino-3-(2-cyclo-pentylphenoxy)-2-propanol-sulfate (penbutolol, Hoe 893d) was studied in patients (n = 36) suffering from primary hypertension in comparison to the effect of 750 mg alpha-methyldopa/day. It was demonstrated that the therapeutic effect of both drugs is identical. Furthermore it was shown that the antihypertensive effect of penbutolol under an uncontrolled diet is unrelated to the patient's basal plasma-renin concentration.

Adolescent↗
PubMed1980

Dietary protein intake influences the antihypertensive potency of methyldopa in spontaneously hypertensive rats.

When spontaneously hypertensive rats consumed a single meal before receiving methyldopa (MD), the increase in brain MD levels and the blood pressure reduction varied inversely with the meal's protein content. MD injection elicited a greater reduction in blood pressure (and a larger rise in brain MD) in spontaneously hypertensive rats consuming a protein-free meal than in fasting animals; it induced a smaller fall in blood pressure (and a smaller increase in brain MD) in spontaneously hypertensive rats ingesting a protein-containing meal than in fasting animals. This effect may depend on the large neutral amino acids contained in protein. Ingestion of a food identical in amino acid content to 18% casein, but containing an amino acid mixture instead of protein, also blunted the MD-induced fall in blood pressure. However, consumption of a similar diet, lacking the large neutral amino acids (but not other amino acids), elicited an MD-induced blood pressure reduction similar to that caused by ingesting a protein-free diet. The combined effects of meal consumption and MD injection on brain MD and blood pressure correlated significantly with the serum ration of MD to the sum of the natural large neutral amino acids and not with serum MD alone. Similar effects were also noted with chronic dietary and MD treatments. Thus, dietary protein content can influence significantly the potency of a clinically important amino acid drug that acts within the brain.

Amino Acids↗
PubMed1994

Black cartilage after therapy with levodopa and methyldopa.

A study was undertaken of 14 autopsy cases with pigmented rib cartilage. Twelve of these patients had been treated with levodopa because of Parkinson's disease for at least 6 years, and two had been treated with methyldopa because of essential hypertension for 19 years. Thirty-two percent of the autopsy cases of Parkinson's disease during a recent 70-month period demonstrated pigmented rib cartilage. Only one of them also demonstrated pigmentation of intervertebral disks. No abnormal pigmentation was seen in other sites. The pigment was located in the hyaline matrix of rib cartilage and in necrotic chondrocytes. Levodopa was chromatographically demonstrated within the cartilage of patients with Parkinson's disease, but in both pigmented and unpigmented sites. It is speculated that a pigmented drug metabolite is bound preferentially to the matrix of rib cartilage. Dopa pigmentation only occurs in cartilage and differs in several respects from endogenous and exogenous ochronosis. It appears to be harmless but irreversible.

Aged↗