α-sympathetic receptor stimulation in the brain and hypotensive activity of α-methyldopa

Heise, A; Kroneberg, G.

doi:10.1016/0014-2999(72)90180-x

Cited by 85 publications

(8 citation statements)

References 9 publications

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“…In both the rat and cat, the hypotensive effect of amethyldopa can be antagonised by the central administration of an ot-adrenoceptor blocking drug (Finch & Haeusler, 1973). Also, when amethylnoradrenaline itself is injected into the cerebral ventricle, it causes a greater pressure fall than ot-methyldopa (Heise & Kroneberg, 1972). Furthermore, when administered centrally, only the (-)-isomer of ot-methyldopa lowers blood pressure and only the (-)-isomer is decarboxylated to a-methylnoradrenaline (Henning, 1969).…”

Section: Resultsmentioning

confidence: 99%

The plasma noradrenaline and growth hormone response to alpha‐ methyldopa and clonidine in hypertensive subjects.

Struthers¹,

Brown²,

Adams³

et al. 1985

Brit J Clinical Pharma

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1 The mechanism of the antihypertensive effect of ot-methyldopa was compared with clonidine by administering equipotent single doses of clonidine (0.2 mg) and amethyldopa (750 mg) to nine hypertensive patients. Plasma noradrenaline was followed for 8 h thereafter as an index of peripheral sympathetic activity. 2 a-Methyldopa and clonidine produced the same hypotensive response at 6 and 8 h after dosing with a similar fall in plasma noradrenaline levels at these times. 3 Linear regression analysis between the systolic blood pressure fall and the corresponding plasma noradrenaline fall, showed that the slopes of the two regression lines were similar for a-methyldopa as for clonidine. 4 Equipotent doses of ao-methyldopa and clonidine produce the same fall in plasma noradrenaline. This supports the current hypothesis that an a-methyldopa metabolite acts centrally, like clonidine, to reduce peripheral sympathetic activity.

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Section: Resultsmentioning

confidence: 99%

The plasma noradrenaline and growth hormone response to alpha‐ methyldopa and clonidine in hypertensive subjects.

Struthers¹,

Brown²,

Adams³

et al. 1985

Brit J Clinical Pharma

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“…However, whether acute administration of a-methyldopa decreases plasma renin activity in the same manner as does chronic administration is unknown. Thus, although the major component of the hypotensive action of a-methyldopa appears to be centrally mediated (2)(3)(4)(5), the mechanism by which a-methyldopa acutely lowers plasma renin activity may involve the inhibition of either central or peripheral adrenergic neurons.…”

Section: Halushka Keisermentioning

confidence: 99%

“…It has been postulated (1) that a-methyldopa is converted to a-methylnorepinephrine, a peripheral neurotransmitter less potent than norepinephrine. Recently, evidence that the hypotensive action of a-methyldopa is mediated by the central nervous system has been presented (2)(3)(4)(5).…”

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confidence: 99%

Acute Effects of Alpha-Methyldopa on Mean Blood Pressure and Plasma Renin Activity

Halushka

Keiser

1974

Circulation Research

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a-Methyldopa significantly lowered mean blood pressure and plasma renin activity in dogs anesthetized with sodium pentobarbital. After unilateral ligation of the right renal vessels and contralateral denervation of the kidney, a-methyldopa significantly lowered mean blood pressure but did not change plasma renin activity. It was concluded that a-methyldopa acutely lowers plasma renin activity via an action mediated through the adrenergic nervous system. However, this decrease in plasma renin activity is not responsible for the decrease in mean blood pressure produced by the drug. KEY WORDS anesthesia unilateral renal denervation radioimmunoassay of angiotensin I unilateral nephrectomy dog• a-Methyldopa is an effective antihypertensive agent, but its mechanism of action is not completely understood. It has been postulated (1) that a-methyldopa is converted to a-methylnorepinephrine, a peripheral neurotransmitter less potent than norepinephrine. Recently, evidence that the hypotensive action of a-methyldopa is mediated by the central nervous system has been presented (2-5). Mohammed et al. (6) found that chronic oral administration of a-methyldopa to one hypertensive patient and a group of normotensive volunteers produced a decrease in plasma renin activity. In a further study (7), stimulation of the renal nerves after chronic oral administration of amethyldopa to dogs resulted in a significant attenuation of renin release. Therefore, it has been postulated (7) that part of the antihypertensive effect of a-methyldopa is mediated through a decrease in plasma renin activity and that the decrease in plasma renin activity might be partly due to an effect on the intrarenal baroreceptors or the macula densa.From the Section on Experimental Therapeutics, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland 20014.Dr. Haluska's present address is Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29401.This paper was presented in part at the 25th Annual Meeting of the American Heart Association, Atlantic City, New Jersey, November 1973.Please address reprint requests to Dr. Harry Keiser, Section on Experimental Therapeutics, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland, 20014. Received February 11, 1974. Accepted for publication June 5, 1974. Weidmann et al. (8) found that chronic oral therapy with a-methyldopa significantly lowered plasma renin activity and mean blood pressure in patients with terminal renal failure. They also demonstrated that a-methyldopa is capable of significantly lowering plasma renin activity and mean blood pressure in patients with essential hypertension who have normal or elevated levels of plasma renin activity but not in hypertensive patients who have low levels of plasma renin activity (9).The purpose of the present study was to determine in dogs if a-methyldopa acutely lowers plasma renin activity and mean blood pressure, if the decrease in plasma renin activity is a d...

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“…The enzymatically formed product of p-hydroxyamphetamine, a-methyldopamine, may be further metabolized to amethylnoradrenaline. The latter compound, which is a pharmacologically active central hypotensive metabolite (12), may also function as a false neurotransmitter (13). Because the Km of the catechol-forming enzyme probably exceeds the concentration of p-hydroxyam phetamine, it is unlikely that substantial amounts of a-methyldopamine are normally synthesized.…”

Section: Discussionmentioning

confidence: 99%

Formation of α-Methyldopamine (‘Catecholamphetamine’) from p-Hydroxyamphetamine by Rat Brain Microsomes

Ar¹,

Bv²,

Axelrod³

1979

Pharmacology

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Amphetamine is a sympathomimetic and psychotropic drug which is extensively metabolized in liver and in brain. One of its major metabolites, p-hydroxyamphetamine, is accumulated by cortical and striatal synaptosomes. In order to learn whether p-hydroxyamphetamine can be further metabolized to a catecholamine, a sensitive radioenzymatic assay was developed which couples the formation of the ‘catecholamphetamine’ to rapid O-methylation by catechol-O-methyltransferase in the presence of [³H]-methyl-S-adenosylmethionine. Rat brain microsomes contain a cytochrome P-450-deρendent monooxygenase which synthesizes catecholamphetamine from p-hydroxyamphetamine. The formation of this catechol metabolite may be involved in the development of tolerance in chronic amphetamine use.

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α-sympathetic receptor stimulation in the brain and hypotensive activity of α-methyldopa

Cited by 85 publications

References 9 publications

The plasma noradrenaline and growth hormone response to alpha‐ methyldopa and clonidine in hypertensive subjects.

The plasma noradrenaline and growth hormone response to alpha‐ methyldopa and clonidine in hypertensive subjects.

Acute Effects of Alpha-Methyldopa on Mean Blood Pressure and Plasma Renin Activity

Formation of α-Methyldopamine (‘Catecholamphetamine’) from p-Hydroxyamphetamine by Rat Brain Microsomes

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α-sympathetic receptor stimulation in the brain and hypotensive activity of α-methyldopa

Cited by 85 publications

References 9 publications

The plasma noradrenaline and growth hormone response to alpha‐ methyldopa and clonidine in hypertensive subjects.

The plasma noradrenaline and growth hormone response to alpha‐ methyldopa and clonidine in hypertensive subjects.

Acute Effects of Alpha-Methyldopa on Mean Blood Pressure and Plasma Renin Activity

Formation of &alpha;-Methyldopamine (&lsquo;Catecholamphetamine&rsquo;) from p-Hydroxyamphetamine by Rat Brain Microsomes

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Formation of α-Methyldopamine (‘Catecholamphetamine’) from p-Hydroxyamphetamine by Rat Brain Microsomes