BP Low Mechanism of Action

Pharmacotherapeutic group: antiadrenergic agents.
Pharmacology: Pharmacodynamics: Mechanism of action: It appears that several mechanisms of action account for the clinically useful effects of methyldopa and the current generally accepted view is that its principal action is on the central nervous system. The antihypertensive effect of Methyldopa is probably due to its metabolism to alpha-methylnoradrenaline, which lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline).
Pharmacokinetics: Following oral administration, Methyldopa is variably and incompletely absorbed, apparently by an amino-acid active transport system. The mean bioavailability has been reported to be about 50%. It is extensively metabolized and is excreted in urine mainly as unchanged drug and the O-sulfate conjugate. It crosses the blood-brain barrier and is decarboxylated in the CNS to active alpha-methylnoradrenaline.
The elimination is biphasic with a half-life of about 1.7 hours in the initial phase; the second phase is more prolonged. Clearance is decreased and half-life prolonged in renal impairment. Plasma protein binding is reported to be minimal. Methyldopa crosses the placenta; small amounts are distributed into breast milk.