Monamine Oxidase

Youdim, Moussa B. H.; Finberg, J. P. M.; Tipton, Keith F.

doi:10.1007/978-3-642-46625-0_3

Cited by 67 publications

(40 citation statements)

References 314 publications

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“…To determine whether the effects of disprocynium24 on clearance and spillover depend on the operation of uptakel and/or MAd and COMT, some of the animals were given desipramine (to block uptake1) and/or inhibitors of both MAd and COMT. While inhibition of MAd type A and B was accomplished by pretreatment with both clorgyline and pargyline (Youdim et al 1988), COMT inhibition was achieved by treatment with tolcapone (Friedgen et al 1993). A preliminary account of the present results was communicated to the German Society for Clinical and Experimental Pharmacology and Toxicology (Friedgen et al 1995).…”

Section: Introductionmentioning

confidence: 99%

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

Friedgen

Wölfel

Russ

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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As selective inhibitors of the extraneuronal monoamine uptake system (uptake2) suitable for in-vivo studies were not available, the question of whether uptake2 plays a definite role in vivo is largely unresolved. We attempted to resolve the question by using 1,1'-diisopropyl-2,4'-cyanine iodide (disprocynium24), a novel agent that blocks uptake2 in vitro with high potency. Anaesthetized rabbits were infused with 3H-labelled noradrenaline, adrenaline and dopamine, and catecholamine plasma clearances as well as rates of spillover of endogenous catecholamines into plasma were measured before and during treatment with either disprocynium24 or vehicle. Four groups of animals were studied: group I, no further treatment: group II, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake1) inhibited; group IV, uptake1 as well as MAO and COMT inhibited. Disprocynium24 (270 nmol kg-1 i.v. followed by an i.v. infusion of 80 nmol kg-1 min-1) did not alter heart rate and mean arterial blood pressure, but increased cardiac output by 22% and decreased the total peripheral vascular resistance by 16% with no difference between groups. When compared with vehicle controls, catecholamine clearances (normalized for the cardiac output of plasma) were decreased and spillover rates increased in response to disprocynium24. Although there were statistically significant between-group differences in baseline clearances (which decreased in the order: group I > group II > group III > group IV), the drug-induced clearance reductions relative to vehicle controls were similar in groups I to IV and amounted to 29-38% for noradrenaline, 22-31% for adrenaline and 16-22% for dopamine. Hence, there was still a significant % reduction in catecholamine clearances even after the combined inhibition of MAO and COMT, and there was no increase in the % reduction of clearances after inhibition of uptake1. Noradrenaline spillover increased in response to disprocynium24 in all four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in adrenaline and dopamine spillover was observed in groups II and IV only. The results indicate that disprocynium24 interferes with the removal of circulating catecholamines not only by inhibiting uptake2, but also by inhibiting related organic cation transporters. As disprocynium24 increased the spillover of endogenous catecholamines into plasma even after inhibition of MAO and COMT, organic cation transporters may also be involved in the removal of endogenous catecholamines before they enter the circulation.

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Section: Introductionmentioning

confidence: 99%

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

Friedgen

Wölfel

Russ

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…MAO-A potently deminates 5-hydroxytryptamine (5-HT), norepinephrine (NE), tyramine, and dopamine (DA) and is selectively inhibited by clorgyline. In contrast, MAO-B potently deaminates benzylamine, phenylethylamine, tyramine, and DA and is selectively inhibited by (-)-deprenyl (Johnson 1968;Youdim et al 1983). Previous work has suggested that the antidepressant efficacy of MAOIs is associated with the inhibition of MAO-A, but not MAO-B fLipper et al 1979).…”

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confidence: 99%

“…The MAOIs (e.g., tranylcypromine, phenelzine, isocarboxazid and iproniazid) tested thus far on the DRL 72-s schedule (O'Donnell andSelden 1982, 1983) are known to inhibit both MAO-A and MAO-B (see Finberg and Youdim 1983). MAO-A potently deminates 5-hydroxytryptamine (5-HT), norepinephrine (NE), tyramine, and dopamine (DA) and is selectively inhibited by clorgyline.…”

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confidence: 99%

Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior

Marek

Seiden

1988

Psychopharmacology

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The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11'305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (-)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.

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“…8 Dopamine and tyramine are metabolized by both forms. [9][10][11] Nevertheless, this specificity is relative and the deamination of a given substrate by MAO-A or MAO-B depends not only on the substrate itself but also on the relative concentration of each form of MAO. Histochemical, immunohistochemical and autoradiographic studies have revealed that the two isoforms of MAO also have a distinct regional brain distribution, with MAO-A found primarily in catecholaminergic neurones and MAO-B localized in serotoninergic neurones and glial cells.…”

Section: Introductionmentioning

confidence: 99%

Radiosynthesis of (S)‐5‐methoxymethyl‐3‐[6‐(4,4,4‐trifluorobutoxy)benzo[d]isoxazol‐3‐yl] oxazolidin‐2‐[¹¹C]one ([¹¹C]SL25.1188), a novel radioligand for imaging monoamine oxidase‐B with PET

Bramoullé

Puech

Saba

et al. 2008

Labelled Comp Radiopharmac

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Radiosynthesis of (S)-5-methoxymethyl-3- [6-(4,4,4-trifluorobutoxy) Within a novel series of 2-oxazolidinones developed in the past by Sanofi-Synthé labo, SL25.1188 ((S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)benzo [d]isoxazol-3-yl]oxazolidin-2-one), a compound that inhibits selectively and competitively MAO-B in human and rat brain (Ki values of 2.9 and 8.5 nM for MAO-B, respectively, and ED 50 (rat) : 0.6 mg/kg p.o.), was considered an appropriate candidate for imaging this enzyme with positron emission tomography. SL25.1188 was labelled with carbon-11 (T 1/2 : 20.38 min) in one chemical step using the following process: (i) reaction of [ 11 C]phosgene with the corresponding ring-opened precursor (1.2-2.5 mg) at 1001C for 2 min in dichloromethane (0.5 mL) followed by (ii) concentration to dryness of the reaction mixture and finally (iii) semi-preparative HPLC purification on a Waters Symmetry s C18. A total of 300-500 MBq of [ 11 C]SL25.1188 (> 95% chemically and radiochemically pure) could be obtained within 30-32 min (Sep-pak-based formulation included) with specific radioactivities ranging from 50 to 70 GBq/lmol (3.5-7% decay-corrected radiochemical yield, based on starting [11 C]CH 4 ).Keywords: SL25.1188; carbon-11; phosgene; MAO-B IntroductionMonoamine oxidase (MAO) is an integral protein of outer mitochondrial membranes and occurs in neuronal and nonneuronal cells in the brain and in peripheral organs. 1,2 Two isoforms, termed MAO-A and MAO-B, have been described, each consisting of two subunits 3,4 coded by different genes and with molecular weights of about 59 700 and 58 800 D, 5 respectively. MAOs catalyse the oxidative deamination of both endogenous and exogenous amines 6 with its two isoforms differing in substrate specificity and inhibitor sensitivity. MAO-A preferentially deaminates 5-hydroxytryptamine (serotonin), norepinephrine and epinephrine and is selectively inactivated by low concentrations of clorgyline.7 MAO-B preferentially deaminates phenethylamine and benzylamine and is selectively inhibited by low concentrations of deprenyl.8 Dopamine and tyramine are metabolized by both forms.9-11 Nevertheless, this specificity is relative and the deamination of a given substrate by MAO-A or MAO-B depends not only on the substrate itself but also on the relative concentration of each form of MAO. Histochemical, immunohistochemical and autoradiographic studies have revealed that the two isoforms of MAO also have a distinct regional brain distribution, with MAO-A found primarily in catecholaminergic neurones and MAO-B localized in serotoninergic neurones and glial cells.Fluctuations in functional MAO activity, directly impacting the concentration of neurotransmitters as well as many xenobiotics, have been associated with human diseases such as Parkinson's disease, depression and certain psychiatric disorders, [12][13][14][15][16] reinforcing the potential role of positron emission tomography (PET) to the in vivo and non-invasive study of these enzymes. A few compounds have already been proposed as...

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Monamine Oxidase

Cited by 67 publications

References 314 publications

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior

Radiosynthesis of (S)‐5‐methoxymethyl‐3‐[6‐(4,4,4‐trifluorobutoxy)benzo[d]isoxazol‐3‐yl] oxazolidin‐2‐[¹¹C]one ([¹¹C]SL25.1188), a novel radioligand for imaging monoamine oxidase‐B with PET

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Monamine Oxidase

Cited by 67 publications

References 314 publications

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior

Radiosynthesis of (S)‐5‐methoxymethyl‐3‐[6‐(4,4,4‐trifluorobutoxy)benzo[d]isoxazol‐3‐yl] oxazolidin‐2‐[11C]one ([11C]SL25.1188), a novel radioligand for imaging monoamine oxidase‐B with PET

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Radiosynthesis of (S)‐5‐methoxymethyl‐3‐[6‐(4,4,4‐trifluorobutoxy)benzo[d]isoxazol‐3‐yl] oxazolidin‐2‐[¹¹C]one ([¹¹C]SL25.1188), a novel radioligand for imaging monoamine oxidase‐B with PET