Methylation of norepinephrine and α-methylnorepinephrine in brain

Fuller, Ray W.; Hemrick‐Luecke, Susan K.

doi:10.1016/0006-2952(82)90094-6

Cited by 10 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly, the nature of the substituent in the aromatic ring does not seem to have a major effect on the observed rate of inactivation of monoamine oxidase B by MPTP analogues, although all three analogues tested gave a significantly higher rate of inactivation than MPTP itself. In contrast, the observed rate of inactivation of monoamine oxidase A by 2'-Me-MPTP was over 4 times faster than that by MPTP itself, but 2'-Et-MPTP and 3'-Cl-MPTP proved to be poor mechanism-based inactivators. Thirdly, although the partition coefficients for the inactivation of either type of monoamine oxidase by some dihydropyridiniums were much lower than we [3] or others [9] previously observed with MPTP itself [3,9], none of the compounds yielded a value approaching unity, which would be required for chemical characterization of an adduct formed with the inactivated enzyme.…”

Section: Resultsmentioning

confidence: 74%

“…Fuller & Hemrick-Luecke [4], working with rodent brain mitochondria, independently discovered the time-dependent inactivation of monoamine oxidase by MPTP, but thought that monoamine oxidase A was only reversibly inhibited by this compound. The reason why they failed to observe that the A enzyme is subject to both reversible (competitive) and irreversible (non-competitive) effects may have been due to the experimental conditions used by these workers, including the radiochemical assay based on a single time point.…”

Section: Introductionmentioning

confidence: 99%

“…Thus the monophasic nature of logarithmic plots of the decrease in activity with time observed by several workers [3][4][5] and the similarity of the pseudo-first-order rate constants from the inactivation of monoamine oxidase B by MPTP and MPDP+ [2] have precluded the drawing of conclusions as to whether inactivation of the enzyme occurs during the first or the second two-electron transfer from MPTP or both. Later, the present authors found that, by varying the concentrations of MPTP or of other tetrahydropyridines and of the enzyme, biphasic kinetics become apparent.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines

Krueger

McKeown

Ramsay

et al. 1990

Biochemical Journal

View full text Add to dashboard Cite

I-Methyl-4-phenyl-1 ,2,3,6-tetrahydropyridine (MPTP) and its primary oxidation product, l-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+), are mechanism-based inhibitors of monoamine oxidases A and B. The pseudo-first-order rate constants for inactivation were determined for various analogues of MPTP and MPDP+ and the concentrations in all redox states were measured throughout the reaction. Disproportionation was observed for all the dihydropyridiniums, but non-enzymic oxidation was insignificant. The dihydropyridiniums were poor substrates for monoamine oxidase A and, consequently, inactivated the enzyme only slowly, despite partition coefficients lower than those for the tetrahydropyridines. For monoamine oxidase B, the dihydropyridiniums were more effective inactivators than the tetrahydropyridines. Substitutions in the aromatic ring had no major effect on the inactivation of monoamine oxidase B, but the 2'-ethyl-and 3'-chloro-substituted compounds were very poor mechanism-based inactivators of monoamine oxidase A. It is clear that both oxidation steps can generate the reactive species responsible for inactivation.

show abstract

Section: Resultsmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines

Krueger

McKeown

Ramsay

et al. 1990

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…The drug is chemically closely related to phenylephrine (an α1-adrenergic receptor agonist) and its metabolite, α-methylnorepinephrine, cross readily blood-brain barrier (Evans & Fogel, 1977;Fuller, Snoddy, & Perry, 1981;Fuller, Snoddy, Perry, Bernstein, & Murphy, 1981a;Fuller & Hemrick-Luecke, 1982). In the patients with familial Mediterranean fever (FMF), metaraminol infusion was associated with an increase in plasma dopamine and epinephrine (E) (a dihydroxyphenyl derivative β-adrenergic agent), yet the urinary levels of dopamine, E and metanephrine remained the same (Barakat, Malhas, & Gumaa, 1989).…”

Section: Metaraminolmentioning

confidence: 99%

Mollaret Meningitis may be Caused by Reactivation of Latent Cerebral Toxoplasmosis

Prandota

2009

International Journal of Neuroscience

View full text Add to dashboard Cite

Mollaret meningitis (MM) occurs mainly in females and is characterized by recurrent episodes of headache, transient neurological abnormalities, and the cerebrospinal fluid containing mononuclear cells. HSV-2 was usually identified as the causative agent. Recently, we found that recurrent headaches in non-HIV-infected subjects were due to acquired cerebral toxoplasmosis (CT). The aim of the study was therefore to focus on molecular pathomechanisms that may lead to reactivation of latent CT and manifest as MM. Literature data cited in this work were selected to illustrate that various factors may affect latent CNS Toxoplasma gondii infection/inflammation intensity and/or host defense mechanisms, i.e., the production of NO, cytokines, tryptophan degradation by indoleamine 2,3-dioxygenase, mechanisms mediated by an IFN-gamma responsive gene family, limiting the availability of intracellular iron to T. gondii, and production of reactive oxygen/nitrogen species, finally inducing choroid plexitis and/or vasculitis. Examples of triggers revealing MM and accompanying disturbances of IFN-gamma-mediated immune responses that control HSV-2 and T. gondii include: female predominance (female mice are more susceptible to T. gondii infection than males); HSV-2 infection (increased IFN-gamma, IL-12); metaraminol (increased plasma catecholamine levels, changes in cytokine expression favoring T(H)2 cells responses); probably cholesterol contained in debris from ruptured epidermoid cysts (decreased NO; increased TNF-alpha, IL-6, IL-8). These irregularities induced by the triggers may be responsible for reactivation of latent CT and development of MM. Thus, subjects with MM should have test(s) for T. gondii infection performed obligatorily.

show abstract

“…22 -23 At this stage the functional significance of methylepinephrine is uncertain, but this amine may be involved in the depletion of epinephrine from medullary and anterior hypothalamic nuclei seen after chronic administration of methyldopa. 24 Moreover, the work of Dampney, 23 Blessing et al, 26 and Reis et al 27 suggests that the Cl region, which is important in cardiovascular control, contains high concentrations of epinephrine. More recently Robertson et al 28 have demonstrated that administration of methylepinephrine into either the lateral ventricle or the NTS produces a prolonged antihypertensive effect.…”

Section: Methylepinephrinementioning

confidence: 99%

Effects of methyldopa metabolites on amine transmitters and adrenergic receptors in rat brain.

Louis¹,

Conway²,

Summers³

et al. 1984

Hypertension

View full text Add to dashboard Cite

Studies of catecholamine concentrations in defined nuclei from the anterior hypothalamic-preoptic regions and the medulla oblongata, known to contribute to cardiovascular control, were measured following acute or chronic methyldopa administration. These studies indicated that methyldopa was enzymatic-ally converted to methyldopamine and methylnorepinephrine, and in some areas to methylepinephrine which replaced endogenous epinephrine. The predominant metabolite was methylnorepinephrine, which accumulated in concentrations higher than endogenous norepinephrine levels. ( -)Methylnorepinephrine was found to be 6 times more potent and 75 times more selective for « 2 -adrenergic receptors than ( -) norepinephrine, and it is suggested that this a 2adrenergic receptor action, particularly in the nucleus tractus solitarius, contributes to a major part of the antihypertensive effect of methyldopa. (Hypertension 6 [Suppl II]: 11-40-11-44, 1984) KEY WORDS • methyldopa • a-methyldopamine • a-methylnorepinephrine • « 2 -adrenergic receptors • radioligand receptor assays • rat brain 11-40

show abstract

Methylation of norepinephrine and α-methylnorepinephrine in brain

Cited by 10 publications

References 11 publications

Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines

Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines

Mollaret Meningitis may be Caused by Reactivation of Latent Cerebral Toxoplasmosis

Effects of methyldopa metabolites on amine transmitters and adrenergic receptors in rat brain.

Contact Info

Product

Resources

About