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PubMed2003

Replacement of antipsychotic and antiepileptic medication by L-alpha-methyldopa in a woman with velocardiofacial syndrome.

We report the case of a 23-year-old woman with velocardiofacial syndrome (VCFS) and a history of psychosis and seizures. She had been treated with conventional antipsychotic and antiepileptic drugs for 10 and 3 years, respectively. However, she continued to experience occasional hallucinations and paroxysmal jerking of the extremities. L-alpha-methyldopa 500 mg b.i.d. (later reduced to 250 mg t.i.d.) was added to her regimen. Hallucinations and seizures stopped shortly. Over the course of approximately 1 year, the previous medications were discontinued without recurrence of psychotic and epileptic symptoms. Eventually, improved mental functions and behaviour enabled her transition from living in a licensed residential facility to sharing a private residence with a partner. VCFS is associated with haploinsufficiency of catecholamine-methyltransferase, leading to excessive extraneuronal catecholamine concentrations. Alpha-Methyldopa inhibits catecholamine neurotransmission in a variety of ways. It is possible that the drug compensated for genetically disturbed catecholamine transmission thus achieving beneficial effects in this case.

Abnormalities, Multiple↗
PubMedDate not supplied

Continuous infusion and withdrawal of methyldopa in the spontaneously hypertensive rat.

In conscious spontaneously hypertensive rats, prepared with permanently indwelling abdominal aortic catheters, the effect on heart rate and blood pressure of a 12-day continuous intragastric infusion of methyldopa (200 mg/kg/day) and its withdrawal were studied. Throughout the infusion period, the blood pressure was significantly reduced, whereas slight but consistent tachycardia was observed. After sudden discontinuation of treatment, heart rate and blood pressure returned to the control level. Overshoots in these parameters were not observed. The appearance of blood pressure upswings after methyldopa withdrawal was limited to two to three per hour. These results contrast with the findings obtained earlier by us with continuous infusion and withdrawal of clonidine in the rat. Clonidine induces hypotension and bradycardia during infusion in the SH rat, whereas a marked overshoot in heart rate and a high frequency of blood pressure upswings appear after cessation of treatment.

Animals↗
PubMed1979

Cryptogenic cirrhosis associated with methyldopa.

A 55-year-old woman developed cirrhosis with portal hypertension while taking methyldopa. No other cause for the cirrhosis was evident. In view of the known hepatotoxic effects of methyldopa, a causal relationship is implied. Possible mechanisms of drug toxicity include both immunologic reactions and direct hepatocellular damage by the drug or its metabolites.

Female↗
PubMed1982

Impaired clot retraction in thrombocytopenia due to methyldopa.

We have described a case of thrombocytopenic purpura caused by methyldopa. A methyldopa-dependent antiplatelet antibody as the mechanism of the patient's thrombopenia was suggested by a positive clot retraction inhibition test. This simple in vitro test should be done more often in suspected cases of drug-induced thrombocytopenia.

Clot Retraction↗
PubMed1975

The effect of spironolactone (Aldactone) and methyldopa in low and normal renin hypertension.

The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension. The 28 patients who completed the entire investigation were treated for 30 weeks, divided into 4 treatment periods and 4 placebo periods of equal duration. BP did not fall significantly during the initial placebo period, and at the end of each of the intervening placebo periods it rose to pretreatment levels. A signifcant decrease in mean BP was found during the 4 treatment periods. A fall exceeding 14% was registered in 32% of the patients after methyldopa, 750 mg/day, in 50% of the patients after spironolactone, 200 mg/day, in 89% after combined treatment with both drugs, and in 29% after spironolactone, 100 mg/day. Low renin hypertension was found in 9 of the 28 patients. The average decrease in mean BP after sironolactone, 200 mg/day, methyldopa, 750 mg/day, and after combined treatment did not differ significantly between the low and the normal renin group. The rationale for using diuretics such as spironolactone or thiazide as the basic therapy in essential hypertension is discussed. It is concluded that both are useful in the treatment of essential hypertension and might be used alone or in combination.

Adult↗
PubMed1977

Controlled clinical study on antihypertensive treatment with a diuretic and methyldopa compared with a beta-blocking agent and hydralazine.

Twenty-eight previously untreated patients with essential hypertension were included in a randomized double-blind cross-over study comparing the results of treatment with the established combination of a thiazide and methyldopa (regimen A) with the combination of a beta-receptor blocker and hydralazine (regimen B). Three patients each developed intolerable side-effects on each regimen but they were all treated successfully on the alternative regimen. The remaining 22 patients obtained a significant reduction in BP at rest and during exercise on both treatments, with no significant difference between the two schedules. Heart rate was significantly reduced at rest and during exercise with regimen B, while a significant reduction was also obtained following exercise on regimen A. There was no significant difference between the two regimens as to tolerable side-effects during treatment, which were registered in about 60% of the patients on each scheme. However, 64% of the patients were treated satisfactorily without side-effects on either regimen. It is concluded that the combination of a beta-blocking agent and hydralazine is without obvious advantages compared with the combination of thiazide and methyldopa in obtaining initial BP control in patients with essential hypertension.

Blood Pressure↗
PubMed1980

The effects of bromocriptine in methyldopa treated hypertension.

1. The effects of treatment with the dopaminergic agonist bromocriptine were studied in nine patients with essential hypertension receiving methyldopa as sole therapy. 2. In Phase 1 of the study, the addition of bromocriptine on a single-blind basis caused a significant fall in lying and standing blood pressures. Plasma prolactin fell significantly but there was no significant change in the other biochemical parameters measured. All patients volunteered that they felt a sense of well-being after starting bromocriptine treatment. 3. In Phase 2 of the study the substitution of placebo for bromocriptine in a randomized double-blind trial significantly increased lying and standing blood pressures and plasma prolactin. No consistent or significant changes were observed in methyldopa-induced side-effects following the substitution of placebo for bromocriptine. 4. In Phase 3 of the study, a gradual increase in blood pressure was observed in all patients over a few months after stopping bromocriptine therapy. 5. The significance of these findings in relation to the role played by plasma prolactin and central dopaminergic activity in blood pressure regulation is discussed.

Adult↗
PubMed1983

Factor VIII inhibitor and raised platelet IgG levels associated with methyldopa therapy.

An inhibitor to the plasma coagulation factor VIII and abnormally high levels of platelet associated IgG (PAIgG) were found in a patient whilst on methyldopa. Both these parameters fell on initial withdrawal, but on rechallenge with the drug only the PAIgG rose to the high presenting levels. No inhibitory activity to factor VIIIc could be detected in a concentrated eluate prepared from the patient's platelets. These results may imply that two distinct antibodies were provoked by the administration of methyldopa, but could also be explained by the action of anti VIIIc alone on the patient's platelets.

Aged↗
PubMedDate not supplied

On suppression of ejaculation by Alpha-methyldopa.

Alpha-methyldopa caused inhibition of ejaculation. The cerebral mechanism which induced the inhibition was pursued by determining changes of brain monoamines in dogs. As a result, suppression of the dopaminergic system in the brain by alpha-methyldopa is found to be the origin of the inhibition of ejaculation. This inhibition was recovered by L-dopa with pretreatment with a peripheral decarboxylase inhibitor.

Animals↗
PubMedDate not supplied

Role of the spinal monoaminergic systems in suppression of ejaculation by alpha-methyldopa.

Alpha-methyldopa causes inhibition of ejaculation by suppressing the dopaminergic system in the brain. The spinal mechanism which works together with this brain inhibitory mechanism was persued by determining the changes of spinal monoamines in dogs. As a result, it was found that suppression of the dopaminergic system by alpha-methyldopa is caused also in the spinal cord just as in the brain and that this suppression can be a direct origin of the inhibition of ejaculation.

Animals↗
PubMed1976

Renin unresponsiveness and the effects of oxprenolol, methyldopa and spironolactone in pateints with essential hypertension.

Plasma renin activity (PRA), supine, erect and post-frusemide (1 mg/kg IV) was studied in 51 patients with previously untreated essential hypertension and their age- and sex-matched normotensive controls. Supine PRA, and the rise in PRA in response to the erect posture and frusemide, were significantly less in hypertensives compared to controls. When the hypertensives were arbitrarily divided into lower, mid, and upper subgroups according to supine PRA, the renin responsiveness was similar in each subgroup but significantly less in hypertensives compared to controls, subdivided in the same way. This does not support the existence of a separate "low renin" subgroup. The low supine PRA and reduced response to stimulation appears to be a feature of patients with essential hypertension. Thirty-nine of these hypertensives entered a double-blind cross-over drug trial of oxprenolol, methyldopa and spironolactone. All three drugs were equally effective in lowering the systolic and diastolic blood pressures in all three renin subgroups. Spironolactone caused a greater fall in systolic pressure in the lower renin group than in the other groups. Oxprenolol was the best tolerated drug, with only 5% of patients withdrawing due to side-effects compared to 13% on spironolacone and 29% on methyldopa.

Adult↗
PubMed1960

The pharmacological actions of 3,4-dihydroxyphenyl-alpha-methylalanine (alpha-methyldopa), an inhibitor of 5-hydroxytryptophan decarboxylase.

alpha-Methyldopa (3,4-dihydroxyphenyl-alpha-methylalanine) is an inhibitor of 5-hydroxytryptophan decarboxylase which is effective in vitro and in vivo. The inhibition is complex and shows coenzyme reversal. Evidence is presented that it acts by coenzyme inactivation. Its administration to mice reduced brain 5-hydroxytryptamine but had no effect on noradrenaline. After repeated doses, intestinal 5-hydroxytryptamine concentrations were also reduced. Co-ordinated activity was diminished coincidently with the enzyme inhibition and the reduction in brain 5-hydroxytryptamine. Rectal temperatures were reduced and the possibility that this resulted from inactivity is discussed. Treated animals showed miosis and narrowing of the palpebral fissures. A comparison is drawn between the actions of alpha-methyldopa and reserpine. The present results support the idea that the sedative effects of both drugs are due to the fall in brain 5-hydroxytryptamine concentration that they produce.

Aminoisobutyric Acids↗
PubMed1989

The preparation of a urokinase-AT-III-PGE1-methyldopa complex, and its effects on platelet adhesion, coagulation times, protein adsorption, and fibrinolysis.

Modifications of urokinase by substances possessing useful therapeutic activity permit combined action preparations to be obtained. Here an attempt was made to develop a complex having combined action for therapeutic activity. The possibility of repeatedly modified urokinase with antithrombin-III-methyldopa-prostaglandin E1 had been experimentally demonstrated. The complex was immobilized on albuminated substrate, which showed fibrinolytic, anticoagulant, and antiplatelet effects simultaneously, in addition to the normal antihypertensive action of methyldopa. The complex immobilized substrate also demonstrated an increase in albumin-surface attachment and a reduction in fibrinogen binding. This may be one of the parameters for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. The approaches suggested indicate the possible new ways of creating nonthrombogenic surfaces with wider applications. A better understanding of the mechanism of these complexes are needed in in vivo conditions to correlate these findings.

Animals↗
PubMed1985

Comparison of the use of reserpine versus alpha-methyldopa for second step treatment of hypertension in the elderly.

A retrospective chart analysis was conducted on all new elderly hypertensive patients referred to a community hypertension clinic who were being treated with either reserpine or alpha-methyldopa plus a diuretic. There were no significant differences between the two groups on entry in age, gender, co-morbid diagnoses, or systolic or diastolic blood pressure. There were no significant differences between the two groups in terms of side effects over three years, but the proportion of persons having compliance problems was significantly lower in the reserpine group. Mean diastolic pressures were significantly lower after one, two, and three years, and systolic pressures were lower after one and two years in the reserpine group. Reserpine is at least as effective as alpha-methyldopa in treating hypertension in the elderly and is associated with fewer problems in compliance.

Aged↗
PubMed1995

Lymphoma and methyldopa therapy.

I describe a patient who developed a drug associated lymphoma with methyldopa attributable to hypersensitive reaction. Several forms of immunologic changes have been observed with methyldopa therapy. In general, they have been considered to be hypersensitive changes from the common development of hemolytic anemia, lupus, retroperitoned fibrosis, thrombocytopenia, and hepatitis.

Aged↗
PubMed1977

Methyldopa binding to cells in culture.

Cells from a rat hepatoma grown in culture were found to activate methyldopa to intermediates which are bound irreversibly to cellular proteins. The binding reaction was not inhibited by superoxide dismutase or allopurinol, but was strongly inhibited by ascorbic acid and glutathione. Methyldopa, paracetamol and furosemide were not mutagenic in the Salmonella/mammalian-microsome mutagenicity test.

Acetaminophen↗
PubMed1973

Interaction between levodopa and methyldopa.

The interaction between methyldopa and levodopa was studied in 18 patients with Parkinsonism. Together they produced a fall in blood pressure in doses which when given alone had no effect or only a slight hypotensive effect. Severe hypotension never occurred. It is reasonable to give methyldopa to hypertensive patients on levodopa but the regimen should be initiated in hospital.

Blood Pressure↗