Liberation of p-hydroxynorephedrine from cat spleen by sympathetic nerve stimulation after pretreatment with amphetamine

Thoenen, H.; Hürlimann, A.; Gey, K. F.; Haefely, W.

doi:10.1016/0024-3205(66)90107-x

Cited by 52 publications

(10 citation statements)

References 3 publications

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“…1967; LEWANDER ,1968) and it was concluded (LEWANDER 1968) that p-hydroxyamphetamine might contribute to the changes in tissue CA levels caused by amphetamine. This conclusion was supported by the previous finding of p-hydroxynorephedrine (or a-methyloctopamine) as a metabolite of amphetamine in peripheral NA neurons (GOLDSTEIN & ANAGNOSTE 1965;THOENEN et al 1966). In addition, p-hydroxynorephedrine has been isolated from peripheral adrenergically innervated organs after the administration of p-hydroxyamphetamine (KOPIN 1965).…”

supporting

confidence: 78%

Displacement of Brain and Heart Noradrenaline by p‐Hydroxynorephedrine after Administration of p‐Hydroxyamphetamine

Lewander¹

1971

Acta Pharmacologica et Toxicologica

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After the administration of p-hydroxyamphetamine 20 mg/kg intraperitoneally, there was a 50 per cent decrease in the brain noradrenaline (NA) level and a 70 per cent decrease in the heart NA level at 4-8 hours after the injection. Control levels of brain and heart NA were reached at 96-144 hours after a single dose of the drug, Repeated injections of p-hydroxyamphetamine, 20 mg/kg twice daily for 3 days, caused a depletion of brain and heart NA to about 20 per cent of the control levels. The brain dopamine (DA) level was reduced to 85 per cent of the control level at 1 hour after 20 mgikg of the drug and to 76 per cent after 40 mg/kg. After the repeated injections of p-OH-A, the brain DA was reduced to 70 per cent of the control level. Radioactively labelled p-hydroxynorephedrine w d S isolated from both brain and heart tissue extracts after the administration of p-hydroxyamphetamine-3H. Parahydroxynorephedrine-sH remained in the brain and the heart as long as the NA levels were decreased. The NA deficit in the brain and heart corresponded approximately to the amounts of p-hydroxynorephedrine-3H present in the tissues. In reserpine pretreated rats the amounts of p-hydroxynorephedrine-3H formed in the brain and heart tissues were reduced, indicating that p-hydroxynorephedrine is bound by a reserpine sensitive storage mechanism. Administration of p-hydroxyamphetamine or amphetamine accelerated the disappearance of labelled p-hydroxynorephedrine from the brain and the heart.In rats, parahydroxyamphetamine is the major metabolite of amphetamine (AXELROD 1954;ALLEVA 1963; DRINC et al. 1966;ELLISON et al. 1966). It has been demonstrated that the intraperitoneal administration of p-hydroxyamphetamine causes a decrease in brain and heart NA1 ( M A~R E & BRUNNER 1 ) Abbreviations used: NA = noradrenaline, DA = dopamine, CA = catecholamine(s).

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supporting

confidence: 78%

Displacement of Brain and Heart Noradrenaline by p‐Hydroxynorephedrine after Administration of p‐Hydroxyamphetamine

Lewander¹

1971

Acta Pharmacologica et Toxicologica

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“…can be released as a less potent "false neurotransmitter" (2,3,16). Another false neurotransmitter, metaraminol (m-hydroxynorephedrine) has also shown to have antihypertensive properties in man (17).…”

Section: Discussionmentioning

confidence: 99%

“…1. The known ability of PHN to deplete norephinephrine (NE) (2) and to replace it in the neurosecetory stores (3) suggests that it may be an active metabolite which could interfere with adrenergic neuron function by acting as a false neurotransmitter. This possibility is given credence by evidence of impaired adrenergic neuron function after moderate to large doses of amphetamine (1).…”

Section: Introductionmentioning

confidence: 99%

Effects of a False Neurotransmitter, p-Hydroxynorephedrine, on the Function of Adrenergic Neurons in Hypertensive Patients

Rangno¹,

Kaufmann²,

Cavanaugh³

et al. 1973

J. Clin. Invest.

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A D S T R A C T Previous studies have shown that amphetamine and p-hydroxyamphetamine impair adrenergic transmission, and it has been suggested that this effect is mediated by an active metabolite, p-hydroxynorephedrine (PHN). Studies in experimental animals have shown that PHN can deplete and substitute for norepinephrine (NE) in the transmitter pool, thus meeting the criteria of a false neurotransmitter.The pharmacologic effects of PHN on adrenergic function and NE synthesis were studied in eight hypertensive patients and compared with placebo. Mean erect and supine blood pressure (BP) decreased 22/14 and 9/6 mm Hg, respectively, during PHN 600 mg daily. The post-Valsalva diastolic overshoot was abolished. The pressor sensitivity to tyramine decreased whereas the pressor response to NE was enhanced. A mild natriuresis occurred. The 24 h urinary excretion of catecholamines and catecholamine metabolites during the administration of PHN compared with placebo changed as follows: vanillylmandelic acid (VMA), 42% decrease; NE, 42% decrease; normetanephrine (NM), 400% increase; metanephrine, unchanged; dopamine, 40% decrease; while homovanillic acid was unchanged. The sum of VMA, NE, and NM decreased 23%. The posttreatment urinary excretion of PHN was biexponential with first and second phase half-lives of 13 and 55 h, respectively.

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“…When injected in relatively high doses systemically, amphetamine has consistently decreased endogenous content of brain noradrenaline (Sanan & Vogt, 1962;Baird & Lewis, 1964;Glowinski, Axelrod & Iversen, 1966). Recent studies suggest that amphetamine depletion of adrenaline may be due to its conversion to p-hydroxy-norephedrine (a-methyl octopamine) (Thoenen, Huerlimann. Gey & Haefely, 1966;Groppetti & Costa, 1969;Gessa, Cho, Clay, Tagliamonte & Brodie, 1969).…”

Section: Discussionmentioning

confidence: 99%

Effects of amphetamine derivatives on brain dopamine and noradrenaline

Breese

Kopin

Weise

1970

British J Pharmacology

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Summary1. Intracisternally administered metaraminol, a-methyl-octopamine, a-methylm-tyramine, and a-methyl tyramine were found to lower brain noradrenaline without having an effect on brain dopamine. 2. Amphetamine, mephentermine, and norephedrine had no effect on brain catecholamines after intracisternal injection.3. There was no reduction in brain dopamine content after intracisternal injection of a-methyl-m-tyramine, yet the resulting brain concentration of a-methyl-m-tyramine was several times higher than after intraperitoneal injection of a-methyl-m-tyrosine, which decreased brain dopamine.4. The decreased synthesis of labelled catecholamines from 14C-tyrosine after a-methyl-m-tyrosine suggested that this compound inhibits tyrosine hydroxylase in addition to its action of displacing brain amines.

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Liberation of p-hydroxynorephedrine from cat spleen by sympathetic nerve stimulation after pretreatment with amphetamine

Cited by 52 publications

References 3 publications

Displacement of Brain and Heart Noradrenaline by p‐Hydroxynorephedrine after Administration of p‐Hydroxyamphetamine

Displacement of Brain and Heart Noradrenaline by p‐Hydroxynorephedrine after Administration of p‐Hydroxyamphetamine

Effects of a False Neurotransmitter, p-Hydroxynorephedrine, on the Function of Adrenergic Neurons in Hypertensive Patients

Effects of amphetamine derivatives on brain dopamine and noradrenaline

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