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MAO-B Activity (mao-b + activity)

Distribution by Scientific Domains

Chemistry	50%
Life Sciences	33%

Selected Abstracts

Lipophilicity Plays a Major Role in Modulating the Inhibition of Monoamine Oxidase B by 7-Substituted Coumarins

CHEMISTRY & BIODIVERSITY, Issue 2 2006
Angelo Carotti
Abstract A series of coumarin derivatives (1,22), bearing at the 7-position ether, ketone, ester, carbamate, or amide functions of varying size and lipophilicity, were synthesized and investigated for their in vitro monoamine oxidase-A and -B (MAO-A and -B) inhibitory activities. Most of the compounds acted preferentially as MAO-B inhibitors, with IC50 values in the micromolar to low-nanomolar range. A structure,activity-relationship (SAR) study highlighted lipophilicity as an important property modulating the MAO-B inhibition potency of 7-substituted coumarins, as shown by a linear correlation (n=20, r2=0.72) between pIC50 and calculated log P values. The stability of ester-containing coumarin derivatives in rat plasma provided information on factors that either favor (lipophilicity) or decrease (steric hindrance) esterase-catalyzed hydrolysis. Two compounds (14 and 22) were selected to investigate how lipophilicity and enzymatic stability may affect in vivo MAO activities, as assayed ex vivo in rat. The most-potent and -selective MAO-B inhibitor 22 (=7-[(3,4-difluorobenzyl)oxy]-3,4-dimethyl-1-benzopyran-2(2H)-one) within the examined series significantly inhibited (>60%) ex vivo rat-liver and striatal MAO-B activities 1,h after intraperitoneal administration of high doses (100 and 300,,mol kg,1), revealing its ability to cross the blood,brain barrier. At the same doses, liver and striatum MAO-A was less inhibited in vivo, somehow reflecting MAO-B selectivity, as assessed in vitro. In contrast, the metabolically less stable derivative 14, bearing an isopropyl ester in the lateral chain, had a weak effect on hepatic MAO-B activity in vivo, and none on striatal MAO-B, but, surprisingly, displayed inhibitory effects on MAO-A in both peripheral and brain tissues. [source]

Monoamine oxidase inhibition and neuroprotection by N1 -propargylphenelzine

DRUG DEVELOPMENT RESEARCH, Issue 1 2001
B. Duff Sloley
Abstract The ability of N1 -propargylphenelzine and related N1 -propargylhydrazines to inhibit monoamine oxidase-A (MAO-A) and -B (MAO-B) and to prevent N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)-induced noradrenergic neurotoxicity was examined. N1 -Propargylphenelzine strongly inhibited MAO-A and MAO-B in in vitro assays using rat brain or liver as the enzyme source. In ex vivo studies in rats, both intraperitoneal and oral administration of N1 -propargylphenelzine strongly inhibited brain and liver MAO-A and MAO-B. The extent of ex vivo MAO inhibition and increased levels of noradrenaline and 5-hydroxytryptamine by N1 -propargylphenelzine was comparable to that of phenelzine. Unlike phenelzine, however, N1 -propargylphenelzine did not elevate ,-aminobutryic acid (GABA) concentrations in rat brain. A single intraperitoneal administration of N1 -propargylphenelzine to mice, 1 week prior to sacrifice, reduced DSP-4-induced depletion of noradrenaline in the hippocampus. The brains of N1 -propargylphenelzine-treated mice from the DSP-4 neurotoxicity experiments had normal MAO-B activity, but MAO-A was significantly inhibited; this was in contrast to animals that had received (,)-deprenyl, who showed normal MAO-A activity but a decrease of MAO-B. The present results indicate that N1 -propargylphenelzine may be a useful neuroprotective compound with a long-term in vivo propensity to inhibit MAO-A. Drug Dev. Res. 53:15,21, 2001. © 2001 Wiley-Liss, Inc. [source]

Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006
Karine Guillem
Abstract Although nicotine is considered to be responsible for the addictive properties of tobacco, growing evidence underlines the importance of non-nicotine components in smoking reinforcement. It has been shown that tobacco smoke contains monoamine oxidase (MAO) A and B inhibitors and decreases MAO-A and MAO-B activity in smokers. Here, we investigated the effects of clorgyline hydrochloride (irreversible MAO-A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO-B inhibitor; 4 mg/kg) and the beta-carboline norharmane hydrochloride (reversible MAO-B inhibitor; 5 mg/kg/day) treatments on nicotine self-administration (30 µg/kg/infusion, free base) in rats. Independent of the responsiveness to novelty and locomotor activity stimulation, only clorgyline hydrochloride treatment increased the intake of nicotine in a fixed-ratio schedule (FR5) of reinforcement. When a progressive-ratio schedule was implemented, both clorgyline hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing effects of nicotine, whereas selegiline had no effect. Taken together, these results indicate that MAO-A inhibition interacts with nicotine to enhance its rewarding effects in rats and suggest that other compounds present in tobacco, such as beta-carboline, may also play an important role in sustaining smoking behavior in humans. [source]

Efficient synthesis and formulation of (R)-(,)-[11C]Deprenyl, a selective radioligand for the quantification of MAO-B activity using PET

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2002
Frédéric Dolle
Abstract Carbon-11 labeled (R)-(,)-Deprenyl is the tracer of reference for the quantification of monoamine oxidase (MAO)-B activity with PET. In this paper, its radiosynthesis is re-investigated and oriented towards the preparation of multi-milliCuries of radiotracer. Typically, using no-carrier-added [11C]methyl triflate as the alkylating agent, 140,190 mCi (5.1,7.0 GBq) of (R)-(,)-[11C]Deprenyl was obtained within 30 min of radiosynthesis (including HPLC purification and formulation) with specific radioactivities ranging from 0.8 to 1.2 Ci/,mol (29.6,44.4 GBq/,mol). The high efficiency of these radiosyntheses allows for multi-injection protocols and kinetic approaches for absolute quantification of the tracer. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Promoting effect and recovery activity from physical stress of the fruit of Morus alba

BIOFACTORS, Issue 1-4 2004
Keum Hee Hwang
Abstract We examined the effects of the fruit of M. alba extracts on the changes of the monoamine oxidase (MAO) activities during and after the physical exercise in rat. Each activity was measured by used serotonin(5-HT) and benzylamine as substrate. Lactate dehydrogenase(LDH) activity and the concentrations of lactate in blood which were clinical indexes of physical exercise were also determined to compare with the relation of MAO activities. Those activities during and after the physical exercise have different tendency in each other enzyme. MAO-A activity was sharply decreased with stress by physical activities compared to the normal group, whereas MAO-B activity was increased for 60 minutes after exercise. All of these indexes were recovered to normal state by oral administration of extract of M. alba. These results of this study suggested M. alba may modulate the MAO activities during exercise and promote the capability of physical activities and show anti-stress effect. In general, MAO inhibitors have been used drugs for the purpose of treatment Parkinson's disease, dementia, deprression. These results can apply to produce the health and functional foods that have modulating effects for these diseases. [source]