Norepinephrine depletion

Neuronal norepinephrin depleting agents [50-55-5] C2 H4QN20g Serpasil, Reserpoid... 

Neuronal Norepinephrine Depleting Agents. Reserpine (Table 6) is the most active alkaloid derived from Rauwolfia serpentina. The principal antihypertensive mechanism of action primarily results from depletion of norepinephrine from peripheral sympathetic nerves and the brain adrenergic neurons. The result is a drastic decrease in the amount of norepinephrine released from these neurons, leading to decrease in vascular tone and lowering of blood pressure. Reserpine also depletes other transmitters including epinephrine, serotonin [50-67-9] dopamine [51-61-6] ... 

Kohm, A. and Sanders, V.M., Suppression of antigen-specific Th2 cell-dependent IgM and IgGl production following norepinephrine depletion in vivo., J. Immunol., 162,5299, 1999. 

C. Amphetamine is an indirectly acting adrenomimetic amine that depends on the release of norepinephrine from noradrenergic nerves for its action. Tlius, its effect depends on neuronal uptake (blocked by cocaine) to displace norepinephrine from the vesicles and the availability of norepinephrine (depleted by reserpine). The substitution on the a-carbon atom blocks oxidation by monoamine oxidase. With no substitution on its benzene ring, amphetamine resists metabolism by COMT. 

P.A. Shore, D. Busfield, H.S. Alpers, Binding and release of metaraminol Mechanism of norepinephrine depletion by a-methyl-m-tyrosine and related reagents, J. Pharmacol. Exp. Ther. 146 (1964) 194-199. 

White SR, Bhatnagar RK, Bardo MT (1983) Norepinephrine depletion in the spinal cord gray matter of rats with experimental allergic encephalomyelitis. J. Neurochem. 40 1771-1773. 

Contraindications Usually safe if not taken in overdoses or excessively. Too much, or in sensitive individuals, may case nasal stuffiness, diarrhea, slowed heartbeat, drowsiness, fatigue. Too frequent use may cause weight gain. MAO inhibitions interefere with serotonin- and norepinephrine-depleting action of reserpine. 

Chester AE, Meyers FH. 1988. Central sympathoplcgic and norepinephrine-depleting effects of antioxidants. Proc Soc Exp Biol Med 187 62-68. 

Symptoms of Dopamine/Norepinephrine Depletion, or Sluggish Depression ... 

A. Disulfiram inhibits aldehyde dehydrogenase, leading to accumulation of acetaldehyde after ethanol ingestion. In addition, it inhibits dopamine betahy-droxylase (necessary for norepinephrine synthesis), resulting in norepinephrine depletion at presynaptic sympathetic nerve endings and leading to vasodilation and orthostatic hypotension. 

In an effort to identify those tetrahydroisoquinolines which will inhibit the action of COMT, but will not act as false neurotransmitters, a series of tetrahydroisoquinolines were evaluated as substrates and inhibitors of this enzyme, and were also tested for their ability to stimulate norepinephrine release from mouse hearts in vivo. Methyl substituents at C-2 and C-4 of 6,7-dihydroxytetrahydroisoquinolines had little effect in regard to COMT, but did eliminate the norepinephrine depleting activity. The interesting exception was 6,7-dihydroxy-2,2-dimethyltetrahydroisoquinolinium iodide which was an active depleter of norepinephrine from mouse hearts. ... 

The real picture is considerably more complicated. A number of findings indicate, for example, that norepinephrine depletion only causes a reduction in blood pressure of therapeutic value if it occurs in central neurones. The replacement of norepinephrine by a-methylnorepinephrine in peripheral organs does not bring about any fall in blood pressure [135]. The hypotensive effect of methyldopa and its analogues does not run parallel to the catecholamine depletion caused by these substances in the heart [42]. 

Metaraminol is a sympathomimetic agent employed to raise blood pressure. Grout et al. [58] reported that, when given orally in low doses, metaraminol lowered the blood pressure in several hypertensive patients. Animal experiments [57, 177, 221] have shown that metaraminol and also various analogues [220] cause norepinephrine depletion. Following administration, metaraminol is taken up by adrenergic nerve endings in place of norepinephrine. Of the various optical isomers of metaraminol only the (—)-erythro form is active [199]. 

According to Thoenen et al. [249], 5-hydroxy dopa gives rise to marked norepinephrine depletion in the cat. Its 0-methyl derivative, 4-methoxy-3,5-dihydroxyphenylalanine, exerts a hypotensive effects in animals [245,250]. 

Mustafa and Chandra Rabbits 400 mg Mn02 intratracheally Whole brain Dopamine and norepinephrine depletion, 24 months post innoculation... 

The mechanism of the central hypotensive effects of L-dopa, a-methyldopa and m-tyrosine has been studied with the aid of peripheral decarboxylase inhibitors.56,57 jhe effects of L-dopa on the cardiovascular system have been reviewed.58 A comparative study of the dose-dependent antihypertensive actions, and the norepinephrine-depleting activities, of a-methyltyramine and a-methyloctopamine in renal rats has been published.59... 

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