Methyldopa

Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blood pressure including very high blood pressure resulting in symptoms other medications are typically preferred. It can be given by mouth or injection into a vein. Onset of effects is around 5 hours and they last about a day.
Common side effects include sleepiness. More severe side effects include red blood cell breakdown, liver problems, and allergic reactions. Methyldopa is in the alpha-2 adrenergic receptor agonist family of medication. It works by stimulating the brain to decrease the activity of the sympathetic nervous system.
Methyldopa was discovered in 1960. It is on the World Health Organization's List of Essential Medicines.
Medical uses.
Methyldopa is used in the clinical treatment of the following disorders:
Side effects.
Methyldopa is capable of inducing a number of adverse side effects, which range from mild to severe. Nevertheless, they are generally mild when the dose is less than 1 gram per day. Side effects may include:
Rebound/withdrawal.
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.
Mechanism of action.
The mechanism of action of methyldopa is not fully clear. Although it is a centrally acting sympathomimetic, it does not block reuptake or transporters. It may reduce the dopaminergic and serotonergic transmission in the peripheral nervous system and it indirectly affects norepinephrine (noradrenaline) synthesis.
The S-enantiomer of methyldopa is a competitive inhibitor of the enzyme aromatic -amino acid decarboxylase (LAAD), which converts -DOPA into dopamine. -DOPA can cross the blood brain barrier and thus methyldopa may have similar effects. LAAD converts it into alpha-methyldopamine, a false prescursor to norepinephrine, which in turn reduces synthesis of norepinephrine in the vesicles. Dopamine beta hydroxylase (DBH) converts alpha-methyldopamine into alpha-methylnorepinephrine, which is an agonist of the presynaptic α2-adrenergic receptor causing inhibition of neurotransmitter release.
Pharmacokinetics.
Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.
History.
When methyldopa was first introduced, it was the mainstay of antihypertensive treatment, but its use has declined on account of relatively severe adverse side effects, with increased use of other safer and more tolerable agents such as alpha blockers, beta blockers, and calcium channel blockers. Additionally, it has yet to be associated with reducing adverse cardiovascular events including myocardial infarction and stroke, or overall all-cause mortality reduction in clinical trials. Nonetheless, one of methyldopa's still current indications is in the management of pregnancy-induced hypertension (PIH), as it is relatively safe in pregnancy compared to many other antihypertensives which may affect the fetus.