Alpha-methyldopa

α-Methyldopa is a synthetically produced amino acid that is used as a drug in the treatment of high blood pressure (antihypertensive). α -Methyldopa is a pharmaceutical precursor with the molecular formula C10H13NO4. The mechanism of action of methyldopa is mainly based on an inhibition of the central sympathetic nervous system. For this reason, Methyldopa is also referred to as an antisympathotonic together with other drugs(reserpine, clonidine, moxonidine). α-Methyldopa has an oral bioavailability of about 25% and a half-life of 1.5 hours.

α-Methyldopa is metabolized in the periphery and in the CNS like naturally occurring dopa. Instead of noradrenalin, the wrong transmitter α-methyl-noradrenalin is produced. In contrast to the physiological noradrenaline, this transmitter acts like a α2-selective agonist. Furthermore α-methyl-DOPA causes an inhibition of the enzyme DOPA-decarboxylase. This suppresses the synthesis pathway of dopamine, noradrenaline and adrenaline.

Norepinephrine causes vasoconstriction via activation of adrenoceptors and thus an increase in blood pressure. α -Methyldopa, on the other hand, as a so-called false carrier substance, has a higher affinity to_{α2 receptors} than to_{α1 receptors}, relative to the physiological carrier substance. The activation of presynaptic α2 receptors peripherally reduces the release of noradrenaline. This effect sets in 2-6h after administration and lasts for a period of about 10 - 16 h.

α-Methyldopa belongs (along with clonidine) to the very small group of substances for which there is experience of use during pregnancy. it is the drug of choice for arterial hypertension in pregnancy (eclampsia).

α-Methyldopa is poorly tolerated by humans. Known side effects are fatigue (in > 10 % of patients), dry nasal mucosa and mild gastrointestinal complaints (in 1-10 % of patients) and harmless darkening of the urine on contact with air (< 1% of patients). Further hypotension with orthostatic dysregulation, skin reactions or immune haemolysis. Further central effects are sedative-hypnotic (activation of central α2 receptors) and analgesic effects. Due to inhibition of the synthesis of norepinephrine and dopamine, depression and drug-induced Parkinsonism may occur.

Bradycardia, edema and depressive moods occur in about 1-10 % of patients, liver damage in about 1%.

Dopegyt®; Presinol ^®

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4. Podymow T et al (2008) Update on the Use of Antihypertensive Drugs in Pregnancy. Hypertension 51: 960-969