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PubMedDate not supplied

Central and peripheral autonomic mechanisms involved in the circulatory actions of methyldopa.

Intracisternal (i.c.) and intravenous (i.v.) administration of methyldopa in conscious rabbits produced closely similar changes in hemodynamics, heart rate, and falls in plasma norepinephrine levels. Two weeks after giving i.c. 6-hydroxydopamine (6-OHDA), when there is widespread destruction of central noradrenergic neurons, the effects of i.c. methyldopa virtually were abolished. This suggests that noradrenergic neurons are the major central site of biotransformation into active metabolites. The circulatory and norepinephrine effects of i.v. methyldopa were attenuated but not completely abolished after giving i.c. 6-OHDA. Hence, in the rabbit about 70% of the action of methyldopa was central and about 30% was peripheral in the human therapeutic range of methyldopa concentrations. Preliminary lesion experiments suggest that the A5 nucleus plays an important role in the bradycardia. Two weeks after giving 5,6-dihydroxytryptamine (5,6-DHT) to destroy serotonergic (5HT) neurons the effects of i.c. methyldopa on mean arterial pressure (MAP) and heart rate were attenuated to approximately 50% of control effects. Therefore, some of the central effects of methyldopa apparently are mediated through 5HT pathways. We also compared the effects of i.c. methyldopa with those of i.c. clonidine (an alpha 2-adrenergic receptor agonist) and with the effects of transmitter release from the endings of noradrenergic and 5HT neurons during the first few hours after either 6-OHDA or 5,6-DHT administration. Our findings suggest that after biotransformation of methyldopa its active metabolites increase the activity of the bulbospinal noradrenergic neurons that control MAP and heart rate and reduce the activity of bulbospinal 5HT neurons.

5,6-Dihydroxytryptamine↗
PubMed1982

[Methyldopa-induced autoimmune hemolytic anemia. Course and long-term observations on 11 patients].

Long-term studies on 11 patients suffering from methyldopa-induced autoimmune haemolytic anaemia suggest that this self limitable episode of disturbed immune tolerance is characterized by five main parameters: 1. The autoimmune pathogenic average daily drug dose: Unfortunately, it cannot be estimated exactly due to the individually rather variable absorption of methyldopa (7-62%). The lowest oral dose in our patients was 125 mg daily. 2. The period of autoimmune induction: between the start of the methyldopa administration and the beginning of autoantibody production. It has to be estimated somewhat shorter than the time up to the clinical manifestation of the haemolytic anaemia. This varied over a wide range from 2 to 52 months. 3. The period of the active autohemolysis: between the appearance of pathogenic autoantibodies and the withdrawal of methyldopa. It depends on the recognition of the cause of the disease. In our patients it varied between 2 and 32 weeks. 4. The period of the haematologic remission: between the withdrawal of methyldopa and the normalization of the red blood cell values. It ranged between 4 weeks and 4 months. Contrary to the other parameters, the clinical remission is almost uniform in all patients. It begins immediately when the drug is stopped. This fact suggests that the induction and maintenance of the disease needs a continuous application of methyldopa and its presence in blood and tissue. The normalization of the red blood cell turnover simultaneous with the cessation of therapy, although the direct antiglobulin test remains positive, reveals a change of the autoantibodies into those apathogenic variants known from the majority of methyldopa-induced autoimmunizations. 5. The period of immunologic remission: between the withdrawal of methyldopa and the definite extinction of autoantibody production. It varied between 4 and 12 months. Transition to or later development of an autonomous warm autoantibody anaemia were not observed. The disease remits spontaneously. Its prompt reversibility resembles the same phenomenon in autoantibody anaemias induced by infectious agents. An inhibition of methyldopa-sensitive suppressor-T-cells may initiate the disturbed tolerance disease.

Adult↗
PubMed1970

Distribution and metabolism of L-3-O-methyldopa in rats.

1. After intraperitoneal administration of L-2-(14)C-3-O-methyldopa ((14)C-O-methyldopa) to rats, the amino-acid was distributed evenly in blood, brain, heart, adipose tissue and liver, whereas it accumulated more in the kidney and the pancreas. (14)C-O-methyldopa showed a biological half-life of about 12-13 h in blood, brain and heart.2. The concentration curve of (14)C-O-methyldopa in brain (after increasing doses of the amino-acid) was linear if measured 2 h after administration, but seemed to reach a plateau at the higher doses if determined after 16 h.3. The concentrations of (14)C-O-methyldopa metabolites (mainly homovanillic acid and 4-hydroxy-3-methoxyphenyllactic acid) were low, except in the kidney, and varied according to the tissue.4. Twenty-four hours after administration of (14)C-O-methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main (14)C-homovanillic acid and (14)C-4-hydroxy-3-methoxyphenyllactic acid) and of 5% of unchanged (14)C-O-methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end-products.5. It is concluded that (14)C-O-methyldopa easily penetrates from the blood into various tissues, including brain, and that the majority of the amino-acid undergoes a slow metabolism. The different shape of the concentration curves for (14)C-O-methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino-acid.

Adipose Tissue↗
PubMed1984

Platelet phenol sulfotransferase and erythrocyte catechol-O-methyltransferase activities: correlation with methyldopa metabolism.

Methyldopa is metabolized by sulfate conjugation catalyzed by phenol sulfotransferase (PST), O-methylation catalyzed by catechol-O-methyltransferase (COMT), and decarboxylation catalyzed by aromatic L-amino acid decarboxylase. These experiments were performed to determine whether individual variations in red blood cell (RBC) COMT and platelet PST activities might reflect variations in the metabolism of methyldopa in man. Methyldopa, 3.5 mg/kg, was taken orally by 28 subjects. Blood samples were obtained from these subjects for the assay of platelet PST and RBC COMT activities, and a 24-hr urine sample was collected for the measurement of methyldopa and its major metabolites. Human platelets contain two independently regulated forms of PST. One form is thermolabile (TL), and the other is thermostable (TS). Methyldopa and alpha-methyldopamine are substrates for the TL but not for the TS form of PST. The results of the experiment showed significant correlations between TL platelet PST activity and the proportion of alpha-methyldopamine excreted as a sulfate conjugate, and between RBC COMT activity and the proportion of methyldopa excreted as an O-methyl metabolite. There was no significant correlation, however, between TL platelet PST activity, and the proportion of methyldopa itself excreted as a sulfate conjugate. These results are compatible with the conclusion that differences among subjects in drug metabolizing enzyme activities are one factor responsible for wide individual variations in methyldopa metabolism in man.

Adult↗
PubMed2000

The effect of methyldopa on retinal artery circulation in pre-eclamptic gravidae.

OBJECTIVE: To evaluate the effect of methyldopa on retinal artery circulation in pre-eclamptic gravidae using color Doppler imaging and spectral analysis. METHODS: Fifty-three pre-eclamptic singleton gravidae of gestational age greater than 22 weeks were examined. Patients with sustained hypertension after 1-2 days hospital rest were treated with oral antihypertensive medication, 250-500 mg methyldopa, three to four times a day for a minimum of 5-7 days. The right central retinal arteries were insonated and Doppler waveform values were analysed before and after medication. RESULTS: The change of the maternal heart rate after methyldopa treatment was -3.96 +/- 7.88 beats per min (P = 0.0006). The change of fetal heart rate was not significantly altered. The change of the diastolic arterial blood pressure after treatment was -4.19 +/- 12.36 mmHg (P = 0.0169). In 36 gravidae, in whom hypotensive effects were noted after treatment with methyldopa, the increase in peak velocity, end-diastolic velocity and mean velocity of the retinal artery were 2.41 +/- 2.20 (P < 0.0001); 1.48 +/- 1.23 (P < 0.0001) and 1.70 +/- 1.42 (P < 0.0001), respectively. The decrease in pulsatility index of the retinal artery after treatment with methyldopa was -0.17 +/- 0.22 (P < 0.0001). In the remaining 17 gravidae, in whom no hypotensive effects were noted after treatment with methyldopa, the decrease in end-diastolic velocity and mean velocity were -1.50 +/- 1.70 (P = 0.0022) and -0.98 +/- 1.90 (P = 0.0488), respectively. The increase in pulsatility index was 0.34 +/- 0.30 (P = 0.0003). CONCLUSIONS: In pre-eclamptic gravidae in whom the hypotensive effects were noted after treatment with methyldopa, the mean velocity of the retinal arteries was significantly higher and the mean pulsatility index lower after treatment. We conclude that the hypotensive effect of methyldopa in pre-eclamptic gravidae is associated with a significant decrease in retinal artery vascular resistance.

Adult↗
PubMed1986

The effect of pH and concentration on alpha-methyldopa absorption in man.

An open crossover study of the absorption of alpha-methyldopa has been conducted in normal healthy adult male volunteers in whom a triple lumen perfusion tube had been placed. Three volunteers were perfused on separate occasions with 0.1 mM alpha-methyldopa at pH 4.5, 6.0 and 7.4. Three other volunteers were perfused on separate occasions with 0.1, 1.0 and 10 mM alpha-methyldopa at pH 6.0. Two additional subjects were perfused with 0.1 mM alpha-methyldopa at pH 6.0. Absorption was not a linear function of concentration above 1 mM alpha-methyldopa. There was also a weak trend toward greater absorption near pH 6.0. At higher concentrations of drug in the perfusion solution (10 vs 1 mM), the free fraction of alpha-methyldopa in plasma samples was increased significantly. Thus, although absorption of alpha-methyldopa is more efficient at lower concentrations, bioavailability may not be substantially enhanced due to increased sulphation in the gut wall. Comparison of permeabilities with previous results from our laboratories suggests the rat is a good model for predicting the behaviour of alpha-methyldopa after its oral administration to man.

Adult↗
PubMed1979

Electrophysiologic properties of methyldopa in man.

There is little information on the effects of methyldopa on the human conduction system. His bundle ECGs were obtained in 11 patients before and after the intravenous infusion of 100 mg of methyldopa. Antegrade refractory periods were obtained with the extrastimulus method. The significant results were as follows: the sinus rate was 71 +/- 4 beats per minute before, and 65 +/- 3 beats per minute after methyldopa (P less than 0.01). The mean A-H interval at a paced rate of 120 beats per minute was 113 +/- 14 msec before, and 135 +/- 18 msec after, methyldopa (P less than 0.05). The mean atrioventricular nodal functional refractory period was 430 +/- 23 msec before and 452 +/- 24 msec after methyldopa administration (P less than 0.001). The mean effective refractory period was 385 +/- 29 msec before, and 388 +/- 27 msec after methyldopa (P less than 0.01). The sinus node recovery time in the control state was 989 +/- 55 msec and 1102 +/- 66 msec after methyldopa infusion (P less than 0.05). Thus, methyldopa can impair conduction through the atrioventricular node and depress the sinus node.

Adult↗
PubMed1984

Comparison of long-term renal hemodynamic effects of methyldopa and propranolol in patients with hypertension and renal insufficiency.

Studies were carried out in 15 patients with renal insufficiency and hypertension to compare the long-term effects of methyldopa and propranolol on renal hemodynamics. Inulin and PAH clearance measurements were made under baseline conditions and four to six months of antihypertensive therapy with each of the two drugs. Eight of the 15 patients (group I) were started on methyldopa and then switched to propranolol; and in the other seven (group II), the sequence was reversed. There were no statistical differences in blood pressure or inulin or PAH clearances under baseline conditions between the two groups of patients. Blood pressure was controlled equally with the two drugs in combination with furosemide. In group I, there was no significant effect of either antihypertensive drug on inulin clearance, but PAH clearance was significantly higher during methyldopa than propranolol therapy. In group II, the same higher PAH clearance was found with methyldopa, even though the sequence of drug administration was opposite to that of group I. Challenge with iv furosemide resulted in a greater 3-hour natriuresis during methyldopa than propranolol treatment. The observations indicate that glomerular filtration rate (GFR) is not significantly affected by long-term treatment with methyldopa or propranolol but that renal plasma flow (RPF) is higher during treatment with methyldopa in patients with renal insufficiency and hypertension. The higher RPF apparently enhances the acute natriuretic effect of iv furosemide.

Adult↗
PubMed1991

Antihypertensive efficacy of guanfacine and methyldopa in patients with mild to moderate essential hypertension.

Guanfacine, an alpha-2 adrenoceptor agonist, was compared with methyldopa as step-2 therapy for patients with mild-to-moderate essential hypertension in a 12-week, double-blind, randomized, parallel evaluation of efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with a diuretic (phase II), and a 12-week treatment period with a diuretic plus methyldopa or guanfacine (phase III). Patients were weaned from prior anti-hypertensive medication during the screening/weaning period and began receiving chlorthalidone 25 mg every morning. Patients received only 25 mg of chlorthalidone each morning during the phase II period. Those who had an average seated diastolic blood pressure (BP) of 95-114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus guanfacine, 1 mg every night, or methyldopa, 250 mg tid. Seated and standing systolic and diastolic BP and pulses were measured biweekly for 12 weeks after randomization. Of the 112 patients who were randomly assigned to guanfacine or methyldopa, 87% completed the entire study. The mean seated systolic and diastolic BP were reduced 13/13 mm Hg by guanfacine administration and 15/13 mm Hg by methyldopa administration. No significant changes in seated pulse were seen in either group. Similar changes occurred in the standing position. Very few adverse effects were reported during the study, the most prevalent side effect was xerostomia (13% guanfacine, 9% methyldopa). No significant differences were observed between treatment groups for the incidence of cardiac arrhythmias after methyldopa or guanfacine administration was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

HPLC for urinary catecholamines and metanephrines with alpha-methyldopa.

In five healthy selected volunteers with normal blood pressure and one pheochromocytoma patient, high performance liquid chromatography (HPLC) has been evaluated, with electrochemical detection for quantitation of urinary catecholamines and metanephrines during administration of the antihypertensive, alpha-methyldopa. The clinical usefulness of HPLC is compared with that of the conventional assay method--the trihydroxyindole (THI)-fluorometric procedure. The THI fluorometric method is known to suffer from true false-positive interference as a result of its inability to differentiate between alpha-methyldopa, its primary metabolic derivatives, and the structurally similar endogenous catecholamines. It is shown that the HPLC separation methodology yields accurate, reproducible results devoid of interference from the presence of alpha-methyldopa. Free urinary excretion rates of epinephrine, norepinephrine, and dopamine were elevated by alpha-methyldopa, P less than 0.001, for epinephrine, norepinephrine, and dopamine when measured by the trihydroxyindole technique but not with high performance liquid chromatography. With alpha-methyldopa treatment, urinary normetanephrine excretion rates were slightly increased, P less than 0.05, by fluorometric analysis and slightly decreased. P less than 0.05, when measured by HPLC. Of added interest, the formation of the normetanephrine analog of alpha-methyldopa, previously undetected, is suggested. Slightly elevated metanephrine levels are seen by the THI-fluorometric method in the presence of alpha-methyl metanephrines. Establishing that the HPLC assay procedure is suitable for clinical diagnosis of pheochromocytoma, despite the presence of alpha-methyldopa, makes it unnecessary to discontinue use of this antihypertensive in screening for pheochromocytoma.

Adult↗
PubMed1982

Duration of effect of single daily dose methyldopa therapy.

1 Methyldopa has a short plasma half-life, but longer duration of antihypertensive effect. A single bedtime dose of methyldopa has been recommended to improve compliance and decrease side effects. 2 This double-blind crossover study was designed to determine the duration of antihypertensive effect of methyldopa by comparing hourly supine and standing blood pressures, throughout the day during placebo, single morning dose, and single evening dose methyldopa therapy in 10 patients. The major side effects, drowsiness and dry mouth were assessed by visual analogue scale. Exercise blood pressures were measured 6, 12, 18 and 24 h after the dose. 3 The antihypertensive effect of methyldopa peaked after 6-9 h and declined thereafter with a half-life of approximately 10 h. Little antihypertensive effect remained 24-26 h after the dose. The time course of the reduction in blood pressure during exercise and of the major side effects paralleled the antihypertensive effects. 4 The results suggest that the duration of antihypertensive effect of methyldopa is long enough to permit twice daily dosing, but that single daily dosing cannot be recommended for most patients. The study illustrates the importance of knowing the time of the last methyldopa dose when assessing blood pressure measurements in patients taking the drug.

Adult↗
PubMed1977

Atenolol, methyldopa, and chlorthalidone in moderate hypertension.

Combined treatment with low doses of different drugs is widely used for moderate hypertension. The effects of atenolol and methyldopa at two dose levels and in combination at the lower doses were studied in patients with moderate hypertension on continuous treatment with moderate hypertension on continuous treatment with chlorthalidone. The mean reduction in standing blood pressures obtained with atenolol 150 and 300 mg/day was about 27/17 mm Hg and with methyldopa 750 and 1500 mg/day about 28/14 mm Hg. Combined treatment with atenolol 150 mg/day and methyldopa 750 mg/day for four weeks resulted in a reduction of 38/25 mm Hg. No difference was observed between the two doses of methyldopa. The lower dose of atenolol was better than the lower dose of methyldopa in reducing lying and standing diastolic blood pressures. These findings show that in patients on continuous treatment with chlorthalidone the addition of atenolol alone or methyldopa alone or of atenolol and methyldopa in combination is effective in the treatment of moderate hypertension.

Adrenergic beta-Antagonists↗
PubMed1976

Methyldopa and propranolol or practolol in moderate hypertension.

The effect of a low dose of methyldopa combined with (a) a non-selective and (b) a selective beta-adrenoceptor antagonist was studied in a double-blind crossover trial in 24 carefully selected patients with moderate hypertension (mean initial lying blood pressure 189/117 mm Hg). Each patient received methyldopa 750 mg/day, propranolol 240 mg/day, practolol 600 mg/day, methyldopa 750 mg/day combined with propranolol 240 mg/day, methyldopa 750 mg/day combined with practolol 600 mg/day, and placebo for four weeks each according to a random sequence. After four weeks of therapy the most effective treatment, methyldopa combined with propranolol, reduced lying and standing blood pressures by 36-5/21-4 mm Hg and 44-7/25 mm Hg respectively. Thic combination had similar effects to those of the combination of methyldopa with the cardioselective agent practolol except that it reduced lying diastolic pressure further. The combination was more effective than either treatment alone. No significant differences were found between the effects of propranolol, practolol, or methyldopa at the doses used.

Adult↗
PubMedDate not supplied

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

Chemical stimulation of brain cholinergic neurons in many species can produce hypertension. Recent studies in this laboratory have demonstrated that clonidine inhibits this central cholinergic pressor response by inhibiting the biosynthesis of brain acetylcholine. This study was designed to determine whether methyldopa, like clonidine, could inhibit brain cholinergic neurons involved in cardiovascular regulation in freely-moving spontaneously hypertensive rats (SHR). Intravenous (i.v.) injection of methyldopa (50-200 mg/kg) produced a dose-related fall in blood pressure (29/15-54/33 mm Hg) in SHR. Intracerebroventricular (i.c.v.) injection of hemicholinium-3 (HC-3) in SHR evoked a fall in arterial pressure through inhibition of acetylcholine synthesis. Doses of HC-3 (10 micrograms, or 15 micrograms, i.c.v.) and methyldopa (50 mg/kg, i.v.) were administered to produce small reductions in arterial pressure in SHR (7-14 mm Hg diastolic, respectively). When the two agents were injected simultaneously, however, a greater than additive response was obtained (p less than 0.05). Central injection of echothiophate (a long-acting cholinesterase inhibitor) to potentiate brain cholinergic activity resulted in a sustained hypertensive response (greater than 40 mm Hg) in SHR for at least 150 minutes. Simultaneous injection of or pretreatment with methyldopa (100 mg/kg, i.v.) inhibited the pressor response to echothiophate over a time course similar to its antihypertensive response in untreated SHR. Methyldopa, however, was completely ineffective in altering the hypertensive response to central injection of carbachol (1 microgram, i.c.v.). This difference in methyldopa susceptibility between the indirect-acting (echothiophate) and direct-acting (carbachol) cholinergic agonists may be related to an inhibiting effect of methyldopa on brain acetylcholine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of alpha-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after alpha-methyldopa administration and remained so for the ensuing 7 hours of the study (p less than 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p less than 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 mumol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by alpha-methyldopa, and the catecholamine metabolites of alpha-methyldopa, alpha-methylnorepinephrine and alpha-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of alpha-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 mumol to 22.7 mumol (24.7 mumol excreted after placebo). Adding benserazide to the alpha/methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of alpha-methyldopa caused little, if any, further antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1977

Peripheral vascular actions of alpha-methyldopa in the dog.

The aim of these study was to investigate peripheral vascular actions of alpha-methyldopa. The following experimental procedures were used: hind-limb of the dog perfused with the animals own blood or with Krebs solution; nictitating membrane of the dog; isolated and perfused segments of the saphenous vein of the dog; superfused strips of the saphenous vein of the dog. In these preparations, effects of alpha-methyldopa on responses elicited by electrical stimulation and on release of 3H-noradrenaline were studied. In dogs pretreated with alpha-methyldopa (200 mg/kg, i.v., 36, 24 and 4 hr before the experiment) contractions of the nictitating membrane caused by cervical sympathetic electrical stimulation were markedly reduced: however, the frequency--response curve to stimulation in the hind-limb and responsiveness to noradrenaline were not significantly different of controls. Perfusion of the hind-limb with Krebs containing alpha-methyldopa (2.2 mM) resulted in a significant reduction of perfusion pressure responses to lumbar sympathetic electrical stimulation with augmented responsiveness to exogenous noradrenaline. Similar results were obtained in in vitro experiments. Effects of alpha-methyldopa were not prevented by cocaine nor by inhibition of decarboxylase by Ro 4-4602 (D,L-serine,2-(2,3,4-,trihydroxybenzyl) hydrazine hydrochloride). Alpha-methyldopa depresses the release of tritiated compounds evoked by electrical stimulation, in saphenous vein strips. This suggests that inhibition of transmitter release could be an important factor to understand peripheral actions of alpha-methyldopa.

Animals↗
PubMed1987

[Maternal effects and perinatal safety of labetalol in the treatment of hypertension in pregnancy. Comparison with methyldopa in a randomized cooperative trial].

Labetalol was compared with methyldopa in a randomised trial involving 176 pregnant women with mild to moderate hypertension. Effective blood pressure control (diastolic pressure below 86 mmHg) was obtained in a similar proportion of mothers given labetalol or methyldopa, but the addition of a complementary treatment to achieve control was less frequently needed in the labetalol than in the methyldopa group (12/91 vs 22/85 p less than 0.05). Side effects were mild and resulted in discontinuation of the randomised treatment in 1 mother given labetalol. Pregnancy was terminated by intrauterine death in 4 mothers given methyldopa, and one neonate born to a patient allocated to labetalol died at day 1. The average birthweight and the proportion of premature delivery or of small for gestational age newborns were similar in both treatment groups. Heart rate, blood pressure, respiratory rate and blood glucose did not differ between infants born to the mothers of the labetalol and the methyldopa groups, irrespective of gestational age at birth or birthweight. Blood pressure control is more frequently achieved in hypertensive pregnancies with labetalol than with methyldopa as a first line treatment. Labetalol is safe to the fetus and newborn and might offer a better prevention of intrauterine death than methyldopa.

Adult↗
PubMed1982

Guanabenz versus methyldopa in the therapy of mild-to-moderate hypertension.

The results of a double-blind cross-over study designed to evaluate the antihypertensive efficacy and safety of guanabenz versus methyldopa in mild-to-moderate essential hypertension are presented. Thirty patients were randomly assigned to a group receiving either guanabenz or methyldopa as initial therapy for 8 weeks, followed by a 2-week wash-out period; the patients then took the other trial medication for 8 weeks. There was a significant fall in both standing and supine systolic and diastolic blood pressures during each treatment period, but no statistically significant difference between the guanabenz and methyldopa periods. However, there was a significant difference between the two drugs as regards side-effects. In the guanabenz group 21% of patients stopped taking the drug because of side-effects or inefficacy compared with none of the patients in the methyldopa group. The overall incidence of adverse experiences was 76% for guanabenz and 50% for methyldopa. There was a statistically significantly greater incidence of dry mouth with guanabenz then with methyldopa, while drowsiness was common in both groups. It is concluded that guanabenz is as effective as methyldopa in the therapy of mild-to-moderate essential hypertension but that the side-effects, particularly dry mouth, will seriously limit its usefulness.

Adult↗