-methyldopa a-甲基多巴 a-methyldopa is a prodrug.It enters into adrenergic neurons and is converted by two enzymes to a-methylnorepinephrine,which has the antihypertensive effect. Mechanism of action:The metabolite,a-methylnorepinephrine,is stored in neurosecretory vesicle in place of NE.When released,a-methyl-NE is a potent a-AR agonist and in PNS is a vasoconstrictor.Its CNS effect is mediated by a2- AR(an autoreceptor),resulting in reduced adrenergic outflow from the CNS and an overall reduced total peripheral resistance. Therapeutic use:This drug does not alter most of the cardiovascular reflexes Cardiac output and blood flow to vital organs are maintained.It reduces renal vascular resistance and can be used in patients with renal insufficiency.Given orally:effect reaches max.in 4-6 h and continues to 24 h.Not used as first drug in monotherapy,but effective when used with diuretics. Adverse effects and toxicity:Sedation,lassitude,nightmares,lactation(due to inhibition of dopaminergic neuron in hypothalamus).Long-term use may cause development of autoantibodies against Rh locus and give positive Coomb's test. 99 α-methyldopa α-甲基多巴 α-methyldopa is a prodrug. It enters into adrenergic neurons and is converted by two enzymes to α-methylnorepinephrine, which has the antihypertensive effect. HO HO CH3 NH2 C COOH H H C HO HO CH3 NH2 C NH2 H H C HO HO CH3 NH2 C NH2 OH H C Aromatic L-amino acid α-methyldopamine α-methylnorepinephrine decarboxylase Dopamine β-oxidase α-methyldopa Mechanism of action: The metabolite, α-methylnorepinephrine, is stored in neurosecretory vesicle in place of NE. When released, α-methyl-NE is a potent α-AR agonist and in PNS is a vasoconstrictor. Its CNS effect is mediated by α2- AR (an autoreceptor), resulting in reduced adrenergic outflow from the CNS and an overall reduced total peripheral resistance. Therapeutic use: This drug does not alter most of the cardiovascular reflexes. Cardiac output and blood flow to vital organs are maintained. It reduces renal vascular resistance and can be used in patients with renal insufficiency. Given orally; effect reaches max. in 4-6 h and continues to 24 h. Not used as first drug in monotherapy, but effective when used with diuretics. Adverse effects and toxicity: Sedation, lassitude, nightmares, lactation (due to inhibition of dopaminergic neuron in hypothalamus). Long-term use may cause development of autoantibodies against Rh locus and give positive Coomb’s test