Decarboxylase Inhibition and Blood Pressure Reduction by α-Methyl-3,4-Dihydroxy-DL-phenylalanine

Oates, John A.; Gillespie, Louis J.; Udenfriend, Sidney; Sjoerdsma, Albert

doi:10.1126/science.131.3417.1890

Cited by 257 publications

(48 citation statements)

References 6 publications

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“…[22][23][24] α-MD is a 3,4-dihydroxyphenylalanine decarboxylase inhibitor which hampers synthesis of catecholamines and 5-HT. [25][26][27] α-MD gives rise to "false transmitters;" α-methyldopamine and α-methylnoradrenaline. 27,28 Presynaptic feedback inhibition of NE occurs since these false transmitters are powerful α 2 -adrenoceptor agonists.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Mante

Woode

Kukuia

et al. 2015

Int J Basic Clin Pharmacol

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Section: Discussionmentioning

confidence: 99%

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Mante

Woode

Kukuia

et al. 2015

Int J Basic Clin Pharmacol

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“…This effect was subsequently confirmed pharmacologically (Reichel and Dengler, 1958). Inhibition of 5-hydroxytryptophan, tyrosine, and tryptophan decarboxylation was also demonstrated (Oates et al, 1960). On administration of methyldopa to hypertensive patients it immediately proved to be an antihypertensive agent (Oates et al, 1960).…”

Section: Methyldopa In the Treatment Of Hypertensionmentioning

confidence: 99%

“…Inhibition of 5-hydroxytryptophan, tyrosine, and tryptophan decarboxylation was also demonstrated (Oates et al, 1960). On administration of methyldopa to hypertensive patients it immediately proved to be an antihypertensive agent (Oates et al, 1960). This warranted a more extensive study in order to assess its value either as a sole agent or in combination with other drugs in the treatment of hypertension.…”

Section: Methyldopa In the Treatment Of Hypertensionmentioning

confidence: 99%

Methyldopa for Treatment of Hypertension

Gilmore¹,

Freis²

1963

JAMA

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ABORTION RATEMEDICALBJOURNsL 295 cause of spontaneous abortion, which still remains unknown. Although only six of the abortuses have been recovered for detailed study, four of them were grossly abnormal. The abnormalities were distributed evenly between patients who received either solution A or solution B. It remains to be determined whether these abnormalities are environmentally or genetically determined.It has taken over three years to collect the 50 cases published in this paper, and because of this relatively small number the investigation will continue to ensure that small, but perhaps ultimately significant, differences do not escape detection. (Goldenberg et al., 1948), although evidence for increased production of these adrenergic amines is absent in most forms of hypertension (von Euler, 1956). SummaryIrrespective of the exact role of catecholamines in hypertension, control of their endogenous production might provide a means of lowering blood-pressure. Methyldopa is a compound shown in vitro to be an effective inhibitor of the decarboxylation of dihydroxyphenylalanine, a precursor of catecholamines (Sourkes, 1954). This effect was subsequently confirmed pharmacologically (Reichel and Dengler, 1958). Inhibition of 5-hydroxytryptophan, tyrosine, and tryptophan decarboxylation was also demonstrated (Oates et al., 1960). On administration of methyldopa to hypertensive patients it immediately proved to be an antihypertensive agent (Oates et al., 1960). This warranted a more extensive study in order to assess its value either as a sole agent or in combination with other drugs in the treatment of hypertension. Possible toxic effects of the drug on the liver, kidneys, and blood picture, and certain aspects of the catecholamine metabolism during administration of methyldopa, have been studied. Materials and MethodsTwenty-eight subjects with persistent hypertension were selected for this study, their ages ranging from 22 to 72 (average 46 Twenty-three hypertensive patients received the drug during their stay in hospital, their blood-pressure being taken three to five times daily in both the recumbent and the standing position. After two days in hospital a placebo capsule was given three times daily for two days to seven patients, after which they received methyldopa capsules on a similar schedule in daily doses ranging from 750 to 2,750 mg. for 2 to 10 days. When necessary the dose was increased every third day.Fourteen subjects were started immediately on methyltWe are grateful to Dr. K. C. Mezey, of Merck Sharpe and Dohme International, for supplying the aldomet used in this study.

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“…Alpha-methyldopa (a-MD) has been shown to be a centrally acting [1,6,9] antihy pertensive agent [4,7,17], The site of this action was shown to be the level of the nucleus tractus solitarii in the medulla oblon gata [16,32]. Furthermore, the action is me diated by a-noradrenergic receptors [16].…”

Section: Introductionmentioning

confidence: 99%

Effect of α-Methyldopa on α-Noradrenergic Receptor Binding Sites in the Mouse Brain

Oide¹

1984

Pharmacology

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α-Methyldopa (α-MD) was administered intraperitoneally into adult male mice and its effect on α₁- and α₂-noradrenergic receptor binding sites in the brain was investigated, using [³H]WB-4101 and [³H]clonidine, respectively. A single injection of 50–200 mg/kg α-MD abolished the high affinity binding to α₂-receptor sites and only the low affinity binding was observed with lower B_max values. A significant effect of α-MD on α₁-receptor sites was not detected even after repeated injections (200 mg/kg/day × 3). Pretreatment with fusaric acid or diethyldithiocarbamate (inhibitors of dopamine-β-hydroxylase) exerted no influence on the actions of α-MD on α₂-receptor sites, whereas NSD-1055 (an inhibitor of dopa decarboxylase) inhibited the effects of α-MD. It is concluded, therefore, that α-methyldopamine, a decarboxylated metabolite of α-MD, may be responsible for the reducing effect of α-MD on α₂-receptor sites.

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Decarboxylase Inhibition and Blood Pressure Reduction by α-Methyl-3,4-Dihydroxy-DL-phenylalanine

Cited by 257 publications

References 6 publications

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Methyldopa for Treatment of Hypertension

Effect of α-Methyldopa on α-Noradrenergic Receptor Binding Sites in the Mouse Brain

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Decarboxylase Inhibition and Blood Pressure Reduction by α-Methyl-3,4-Dihydroxy-DL-phenylalanine

Cited by 257 publications

References 6 publications

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Methyldopa for Treatment of Hypertension

Effect of &alpha;-Methyldopa on &alpha;-Noradrenergic Receptor Binding Sites in the Mouse Brain

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Effect of α-Methyldopa on α-Noradrenergic Receptor Binding Sites in the Mouse Brain