メチルドパ

A: α-Methyldopa is a centrally acting antihypertensive agent. It is converted to α-methylnorepinephrine in the brain, which then acts as an agonist at central α2-adrenergic receptors. [] This activation reduces sympathetic outflow from the brain, leading to a decrease in peripheral vascular resistance and blood pressure. [, , ]

A: While its primary action is central, α-Methyldopa does have some peripheral effects. Studies in rabbits suggest that about 70% of its action is central, while 30% is attributed to peripheral mechanisms. [] Peripherally, α-methylnorepinephrine can act as a false neurotransmitter, competing with norepinephrine at sympathetic nerve endings. This can contribute to its antihypertensive effect, particularly at lower frequencies of sympathetic nerve stimulation. [, ]

A: Research indicates that some of α-Methyldopa's central effects might be mediated through serotonin pathways. Experiments in rabbits showed that destroying serotonergic neurons with 5,6-dihydroxytryptamine attenuated the effects of centrally administered α-Methyldopa on mean arterial pressure and heart rate by approximately 50%. []

A: Studies suggest that β-adrenergic receptor stimulation might play a role in the overall effects of α-Methyldopa. Metabolites of α-Methyldopa have shown high potency in competing for β1 receptors in the forebrain. Additionally, (-)-erythro-α-methylepinephrine, a α-Methyldopa metabolite, displayed a higher potency than (-)-epinephrine, (-)-norepinephrine, and (-)-erythro-α-methylnorepinephrine in competing for β2 receptors on human lymphocytes. []

A: The molecular formula of α-Methyldopa sesquihydrate is C10H13NO4 · 1½H2O. Its molecular weight is 238.24 g/mol. []

A: α-Methyldopa itself is a prodrug, meaning it is metabolized in the body to its active form, α-methylnorepinephrine. This metabolite is structurally similar to norepinephrine, allowing it to interact with adrenergic receptors. The α-methyl group is crucial for its central activity and reduces its potency at peripheral adrenergic receptors compared to norepinephrine. [, ]

A: One challenge in formulating α-Methyldopa is its susceptibility to oxidation. [] Exposure to air, light, and high pH can degrade the drug, leading to changes in color and efficacy.

A: α-Methyldopa is well absorbed after oral administration. It is primarily metabolized in the liver and central nervous system to α-methyldopamine and α-methylnorepinephrine. [, , ]

A: α-Methyldopa and its metabolites are mainly excreted in the urine. [, , ] Studies in neonates showed that α-Methyldopa is readily metabolized to α-methyldopa sulfate, and both are excreted slowly compared to adults, resulting in a longer half-life. []

A: Studies indicate a potential for dose-dependent metabolism of α-Methyldopa. Research in Parkinson's disease patients revealed that the proportion of the dose excreted as vanillacetic acid (VLA) increased linearly with increasing α-Methyldopa dosage. This suggests a potential induction of the transaminase enzyme involved in its metabolism. []

A: Yes, α-Methyldopa has been shown to interact with iron supplementation. α-Methyldopa can form complexes with both ferrous and ferric iron. This interaction is pH-dependent, with complex formation being faster at higher pH levels. The tight binding of ferric iron to α-Methyldopa can potentially alter the drug's biodistribution. Furthermore, under the acidic conditions of the stomach, redox cycling can occur, leading to both catechol oxidation and the production of potentially harmful hydroxyl radicals. Therefore, caution is advised when administering α-Methyldopa concurrently with ferrous sulfate. []

A: α-Methyldopa consistently demonstrated antihypertensive effects in various animal models. In spontaneously hypertensive rats (SHR), both long-term intravenous infusions and prolonged oral administration of α-Methyldopa significantly reduced mean arterial pressure. [, ] These effects are consistent with its mechanism of action, primarily involving the central nervous system.

A: Research suggests that α-Methyldopa might have a beneficial effect on cardiac hypertrophy associated with hypertension. In SHR, prolonged treatment with α-Methyldopa resulted in significantly reduced cardiac masses and heart weight-to-body weight ratios compared to untreated controls. Interestingly, this effect was not observed with clonidine, another centrally acting antihypertensive. [] Furthermore, α-Methyldopa also reduced cardiac mass in normotensive Wistar Kyoto rats without significantly affecting systemic hemodynamics, suggesting a potential direct effect on cardiac hypertrophy beyond blood pressure reduction. []

A: α-Methyldopa has been associated with several side effects, including drowsiness, dry mouth, headache, and dizziness. [, , ] In rare cases, it can also cause more serious adverse effects like liver damage and hemolytic anemia. [, , ]

A: The impact of α-Methyldopa on GH secretion appears to be more complex and potentially time-dependent. While short-term α-Methyldopa treatment in hypertensive patients did not significantly affect GH levels during an insulin stimulation test, there are suggestions that long-term treatment might have different effects. [] One hypothesis is that the time course of α-Methyldopa's effect on GH secretion might be related to the gradual substitution of endogenous catecholamines with α-Methyldopa metabolites within the brain. []

A: Liquid chromatography (LC) is a commonly used method for determining α-Methyldopa concentrations in both pharmaceutical formulations and biological samples. [] Reverse-phase C18 columns, coupled with UV detection, have been successfully employed for this purpose. This method offers high sensitivity and can also be used to quantify α-Methyldopa in combination with other drugs like hydrochlorothiazide and chlorothiazide. []

A: Yes, spectrophotometric methods based on charge-transfer complexation can be used for the determination of α-Methyldopa in pharmaceutical formulations. [] One such method utilizes bromanil as a complexing agent, resulting in a green-colored product with maximum absorbance at 738 nm. This method offers a simple, rapid, and cost-effective approach for α-Methyldopa quantification. []

A: α-Methyldopa has been associated with the development of autoimmune hemolytic anemia in some patients, although this is a rare side effect. [, ] The mechanism is not fully understood, but it is thought to involve the production of autoantibodies against red blood cells. []

A: Research suggests that α-Methyldopa metabolism might involve COMT. Experiments using dopacetamide, a COMT inhibitor, revealed alterations in the urinary excretion profile of α-Methyldopa metabolites in rats. Dopacetamide administration led to an increase in the urinary content of 14C-3,4-dihydroxyphenylacetic acid and 14C-dopamine, while decreasing 14C-3-methoxytyramine levels. [] This observation suggests that COMT might play a role in the O-methylation pathway of α-Methyldopa metabolism.

ANone: Several alternative antihypertensive medications are available, each with its own mechanism of action and side effect profile. Some commonly used alternatives include:

• Beta-blockers (e.g., metoprolol, propranolol, labetalol): These drugs block the effects of adrenaline on the heart and blood vessels, leading to a decrease in heart rate and blood pressure. [, , , ]
• Calcium channel blockers (e.g., nifedipine, diltiazem): These medications relax and widen blood vessels by blocking the entry of calcium into muscle cells lining the vessel walls. [, ]
• ACE inhibitors (e.g., captopril): These drugs block the action of angiotensin-converting enzyme (ACE), an enzyme that produces angiotensin II, a potent vasoconstrictor. []