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Monoamine Oxidase (monoamine + oxidase)
Terms modified by Monoamine Oxidase Selected AbstractsSynthesis of a 13C labeled N -cyclopropylamine tetrahydropyridine derivativeJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2002Simon Kuttab Abstract The synthesis of 1-(2- 13C)-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine (8) is reported. Attempts were first made to prepare labeled cyclopropylamine via a cyclopropanation/Curtius rearrangement sequence, but the yields were too modest to be suitable for the synthesis of a labeled compound. The preparation of 8 was achieved via cyclopropanation of the N -formyl tetrahydropyridine derivative 21 using the Grignard reagent of ethyl bromide and Ti(O- iPr)4 as a catalyst. The synthesis proceeded in high yield (82%). The method has a wide potential for the synthesis of other cyclopropyl ring labeled and substituted cyclopropyl ring labeled tetrahydropyridine dervatives which can be used in Monoamine Oxidase (MAO) and Cyt P450 enzymes mechanistic studies. Copyright © 2002 John Wiley & Sons, Ltd. [source] ChemInform Abstract: Facile Synthesis of Substituted trans-2-Arylcyclopropylamine Inhibitors of the Human Histone Demethylase LSD1 and Monoamine Oxidases A and B.CHEMINFORM, Issue 42 2008David M. Gooden Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Karine 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] Behavioral genetics in antisocial spectrum disorders and psychopathy: A review of the recent literatureBEHAVIORAL SCIENCES & THE LAW, Issue 2 2010Tracy D. Gunter M.D. Behavioral geneticists are increasingly using the tools of molecular genetics to extend upon discoveries from twin, family, and adoption studies concerning the heritability of antisocial spectrum disorders and psychopathy. While there is a substantial body of research concerning antisocial spectrum disorders in the behavioral genetics literature, only a few studies could be located using the phenotype of psychopathy. In this report we summarize some of the recent molecular genetics work concerning antisocial spectrum disorders and psychopathy, with a focus on genes involved in the serotonergic and dopaminergic pathways, while also mentioning some of the novel genetic factors being considered. Monoamine oxidase (MAOA) and the serotonin transporter (5HTT) are reviewed at length, as these genes have received significant scientific attention in recent years and are sites of high biological plausibility in antisocial spectrum disorders and psychopathy. Copyright © 2010 John Wiley & Sons, Ltd. [source] Monoamine oxidase A and B activities in embryonic chick hepatocytes: differential regulation by retinoic acidCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2002Antonietta Nicotra Abstract Monoamine oxidases (MAOs) A and B are two isoenzymes involved in the degradation of many biological amines in the nervous system and in peripheral organs. In the present work hepatocytes isolated from 14-day-old chick embryos were used as a model system to determine whether retinoic acid (RA) is capable of modulating the activity of the two MAO forms. RA is a retinoid that, by binding with nuclear receptors, interferes with the expression of specific genes in many differentiation processes. Enzymic activity was measured with a radiochemical method using serotonin and ,-phenylethylamine as preferential substrates for MAO A and MAO B, respectively. The specific activity of the two forms was measured in hepatocytes cultured for 24, 48 and 72,h in the presence and the absence of serum. RA stimulated MAO B but not MAO A activity, in a dose- and time-dependent way, and only in the presence of serum. Maximum stimulation (about 3.5-fold) was obtained after treatment with 5,,M RA for 72,h. Kinetic analysis of MAO B activity showed an increase in Vmax in treated hepatocytes (5,,M RA for 72,h) with no change in Km. In conclusion, the present work shows that RA selectively elicits MAO B activity in cultured chick embryonic hepatocytes, this stimulation requires the presence of some factors present in the serum and is probably due to an increase in the number of enzyme molecules. Copyright © 2001 John Wiley & Sons, Ltd. [source] Positron emission tomography and its use to image the occupancy of drug binding sitesDRUG DEVELOPMENT RESEARCH, Issue 2 2003S. John Gatley Abstract The development of positron emission tomography (PET) and the ability to synthesize compounds labeled with the short-lived positron emitters 11C and 18F has made possible the imaging and quantification of drug binding sites in the human body. By conducting PET studies with an appropriate radioligand before and after treatment with a drug, the fraction of the total number of binding sites that is occupied by the drug (the "occupancy" of the site) can often be determined. To the extent that occupancy is a good indicator of pharmacological activity, such PET experiments can aid the development of drug dosage regimens. Some of the general issues involved in PET studies of drug occupancy are discussed. There have been many such studies involving antipsychotic drugs and dopamine D2 receptor radioligands. Since neuroleptics have been extensively reviewed elsewhere, only the major findings are discussed here. Other binding sites (and drug classes) in the dopamine system to which this methodology has been applied include: the dopamine transporter (stimulant drugs) and monoamine oxidase A and B (antidepressant drugs). Occupancy studies are also possible for many drug targets beyond the dopamine system. Drug Dev. Res. 59:194,207, 2003. © 2003 Wiley-Liss, Inc. [source] Genetic and non-genetic influences on the development of co-occurring alcohol problem use and internalizing symptomatology in adolescence: a reviewADDICTION, Issue 7 2009Luca Saraceno ABSTRACT Aims Alcohol problem use during adolescence has been linked to a variety of adverse consequences, including cigarette and illicit drug use, delinquency, adverse effects on pubertal brain development and increased risk of morbidity and mortality. In addition, heavy alcohol-drinking adolescents are at increased risk of comorbid psychopathology, including internalizing symptomatology (especially depression and anxiety). A range of genetic and non-genetic factors have been implicated in both alcohol problem use as well as internalizing symptomatology. However, to what extent shared risk factors contribute to their comorbidity in adolescence is poorly understood. Design We conducted a systematic review on Medline, PsycINFO, Embase and Web of Science to identify epidemiological and molecular genetic studies published between November 1997 and November 2007 that examined risk factors that may be shared in common between alcohol problem use and internalizing symptomatology in adolescence. Findings Externalizing disorders, family alcohol problems and stress, as well as the serotonin transporter (5-HTT) S-allele, the monoamine oxidase A (MAOA) low-activity alleles and the dopamine D2 receptor (DDR2) Taq A1 allele have been associated most frequently with both traits. An increasing number of papers are focusing upon the role of gene,gene (epistasis) and gene,environment interactions in the development of comorbid alcohol problem use and internalizing symptomatology. Conclusions Further research in adolescents is warranted; the increasing availability of large longitudinal genetically informative studies will provide the evidence base from which effective prevention and intervention strategies for comorbid alcohol problems and internalizing symptomatology can be developed. [source] The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumptionADDICTION, Issue 3 2007Kent W. Nilsson ABSTRACT Aim To investigate possible interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter, family relations and maltreatment/sexual abuse on adolescent alcohol-related problem behaviour among male adolescents. Design, setting and participants A cross-sectional study of a randomized sample of 66 male individuals from a total population of 16- and 19-year adolescents from a Swedish county. Boys, who volunteered to participate answering an alcohol-related problem/behaviour questionnaire, were investigated with regard to interactions between such problems, family function, maltreatment and MAO-A genotype. Measurements MAO-A genotype, family relations history, history of being maltreated or abused and alcohol-related problem behaviour. Findings Boys with the short (three-repeat) variant of the MAO-A gene, who had been maltreated/abused or came from families with poor relations, showed significantly higher scores of alcohol-related problems. We also found that maltreatment/abuse independently showed the strongest relation to alcohol-related problems among boys in our model. Conclusions The results suggest that both maltreatment and MAO-A genotype may be useful for the understanding of male adolescent alcohol-related problem behaviour. [source] PRECLINICAL STUDY: Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type AADDICTION BIOLOGY, Issue 2 2009Ema Alves ABSTRACT The administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ,ecstasy') to the rat results in mitochondrial oxidative damage in the central nervous system, namely lipid and protein oxidation and mitochondrial DNA deletions with subsequent impairment of the correspondent protein expression. Although these toxic effects were shown to be prevented by monoamine oxidase B inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated mitochondrial damage remains to be evaluated. Thus, the aim of the present study was to clarify the potential interference of a specific inhibition of MAO-A by clorgyline, on the deleterious effects produced by a binge administration of a neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations) to an adolescent rat model. The parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation and expression of the respiratory chain protein subunits II of reduced nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome oxidase (COXI). Considering that hyperthermia has been shown to contribute to the neurotoxic effects of MDMA, another objective of the present study was to evaluate the body temperature changes mediated by MDMA with a MAO-A selective inhibition by clorgyline. The obtained results demonstrated that the administration of a neurotoxic binge dose of MDMA to an adolescent rat model previously treated with the specific MAO-A inhibitor, clorgyline, resulted in synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, provoking high mortality. Inhibition of MAO-A by clorgyline administration had no protective effect on MDMA-induced alterations on brain mitochondria (increased lipid peroxidation, protein carbonylation and decrease in the expression of the respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced decrease in the expression of COXI. These results reinforce the notion that the concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the resulting severe synergic toxicity. [source] Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Karine 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] The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathwaysEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003C. M. Vacher Abstract Nitric oxide (NO) is known to regulate the release of arginine-vasopressin (AVP) and oxytocin (OT) by the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). The aim of the current study was to identify in these nuclei the NO-producing neurons and the NO-receptive cells in mice. The determination of NO-synthesizing neurons was performed by double immunohistochemistry for the neuronal form of NO synthase (NOS), and AVP or OT. Besides, we visualized the NO-receptive cells by detecting cyclic GMP (cGMP), the major second messenger for NO, by immunohistochemistry on hypothalamus slices. Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice. By contrast, cGMP was not observed in magnocellular neurons, but in GABA-, tyrosine hydroxylase- and glutamate-positive fibers, as well as in GFAP-stained cells. The cGMP-immunostaining was abolished by incubating brain slices with a NOS inhibitor (L-NAME). Consequently, we provide the first evidence that NO could regulate the release of AVP and OT indirectly by modulating the activity of the main afferents to magnocellular neurons rather than by acting directly on magnocellular neurons. Moreover, both the NADPH-diaphorase activity and the mean intensity of cGMP-immunofluorescence were increased in monoamine oxidase A knock-out mice (Tg8) compared to control mice (C3H) in both nuclei. This suggests that monoamines could enhance the production of NO, contributing by this way to the fine regulation of AVP and OT release and synthesis. [source] Mutagenic probes of the role of Ser209 on the cavity shaping loop of human monoamine oxidase AFEBS JOURNAL, Issue 16 2009Jin Wang The available literature implicating human monoamine oxidase A (MAO A) in apoptotic processes reports levels of MAO A protein that do not correlate with activity, suggesting that unknown mechanisms may be involved in the regulation of catalytic function. Bioinformatic analysis suggests Ser209 as a possible phosphorylation site that may be relevant to catalytic function because it is adjacent to a six-residue loop termed the ,cavity shaping loop' from structural data. To probe the functional role of this site, MAO A Ser209Ala and Ser209Glu mutants were created and investigated. In its membrane-bound form, the MAO A Ser209Glu phosphorylation mimic exhibits catalytic and inhibitor binding properties similar to those of wild-type MAO A. Solubilization in detergent solution and purification of the Ser209Glu mutant results in considerable decreases in these functional parameters. By contrast, the MAO A Ser209Ala mutant exhibits similar catalytic properties to those of wild-type enzyme when purified. Compared to purified wild-type and Ser209Ala MAO A proteins, the Ser209Glu MAO A mutant shows significant differences in covalent flavin fluorescence yield, CD spectra and thermal stability. These structural differences in the purified MAO A Ser209Glu mutant are not exhibited in quantitative structure,activity relationship patterns using a series of para -substituted benzylamine analogs similar to the wild-type enzyme. These data suggest that Ser209 in MAO A does not appear to be the putative phosphorylation site for regulation of MAO A activity and demonstrate that the membrane environment plays a significant role in stabilizing the structure of MAO A and its mutant forms. [source] Mutations in human monoamine-related neurotransmitter pathway genes,HUMAN MUTATION, Issue 7 2008Jan Haavik Abstract Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (D,H), and phenylethanolamine N -methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O -methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org). Hum Mutat 29(7), 891,902, 2008. © 2008 Wiley-Liss, Inc. [source] Ontogenetic effects of MAO-A inhibition on rat pineal n -acetylserotonin and melatonin during the first month of neonatal lifeHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2000Gregory F Oxenkrug Abstract Inhibitors of monoamine oxidase A (MAO-A) but not MAO-B stimulate the activity of pineal serotonin N -acetyltransferase (AANAT) in the adult rat pineal leading to increased formation of N -acetyl serotonin (NAS) and melatonin (MEL). The pineal gland of the neonatal rat has AANAT activity, but the second enzyme in melatonin biosynthesis, HIOMT (hydroxyindole- O -methyltransferase) converting NAS to MEL, is absent during the first week of neonatal life. In this study we examined the effects of acute clorgyline treatment in vitro and in vivo, on pineal indoles over the first month of neonatal life. The results show that clorgyline stimulates NAS production by pineal both in vitro and in vivo from day five on with a marked increase between day 14 and day 21. In contrast, MEL is not increased until day 21, with a sharp rise thereafter. Copyright © 2000 John Wiley & Sons, Ltd. [source] Association of 5-HTT gene polymorphism, platelet MAO activity, and drive for thinness in a population-based sample of adolescent girlsINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 5 2008Kirsti Akkermann MSc Abstract Objective: Several lines of evidence suggest that alterations in serotonergic activity contribute to the pathophysiology of abnormal eating behaviors. Since platelet monoamine oxidase (MAO) activity and the 5-HT transporter gene promoter polymorphism (5-HTTLPR) have been associated with eating disorders, the knowledge from a population-based sample may provide useful information which changes in 5-HT function observed in eating disorders represent trait vs. state effects. Method: The sample was based on both cohorts of the Estonian Children Personality, Behavior and Health Study (ECPBHS). The current study was conducted during the second follow-up where altogether 82% from the original sample was recruited. EDI-2 subscales,Drive for Thinness and Bulimia,were used to determine eating attitudes and behaviors. Platelet MAO activity was measured and the participants were genotyped for the 5-HTTLPR. Results: Allelic variation of 5-HTTLPR or platelet MAO activity were not independently associated with drive for thinness or binge eating, but girls homozygous for the 5-HTTLPR long allele and with high platelet MAO activity, both considered indicators of a higher capacity 5-HT system, exhibited higher scores of drive for thinness. Conclusion: The results suggest that drive for thinness is the highest in girls with the presence of two markers of higher serotonergic capacity. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [source] Monoamine oxidase activity in kidney and heart of Piaractus mesopotamicus (Holmberg)JOURNAL OF FISH BIOLOGY, Issue 6 2007C. M. C. Salles The values of Michaelis,Menten constant (KM) and maximum velocity (VMAX) for kidney and heart monoamine oxidase (MAO) from pacu Piaractus mesopotamicus were determined. The mean ±s.e. KM values were 17·28 ± 2·27 ,M for kidney and 15·38 ± 1·86 ,M for heart. MAO activities were 111·60 ± 3·25 and 15·12 ± 0·30 nmols min,1 g,1 of wet tissue for kidney and heart, respectively. In addition, MAO inhibitory studies in these two tissues indicate that this enzyme may be a different isoform of MAO. [source] Efficient synthesis and formulation of (R)-(,)-[11C]Deprenyl, a selective radioligand for the quantification of MAO-B activity using PETJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2002Frédéric 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] Acute Activation of Hippocampal Glucocorticoid Receptors Results in Different Waves of Gene Expression Throughout TimeJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2006M. C. Morsink Abstract Several aspects of hippocampal cell function are influenced by adrenal-secreted glucocorticoids in a delayed, genomic fashion. Previously, we used Serial Analysis of Gene Expression to identify glucocorticoid receptor (GR)-induced transcriptional changes in the hippocampus at a fixed time point. However, because changes in mRNA levels are transient and most likely precede the effects on hippocampal cell function, the aim of the current study was to assess the transcriptional changes in a broader time window by generating a time curve of GR-mediated gene expression changes. Therefore, we used rat hippocampal slices obtained from adrenalectomised rats, substituted in vivo with low corticosterone pellets, predominantly occupying the hippocampal mineralocorticoid receptors. To activate GR, slices were treated in vitro with a high (100 nM) dose of corticosterone and gene expression was profiled 1, 3 and 5 h after GR-activation. Using Affymetrix GeneChips, a striking pattern with different waves of gene expression was observed, shifting from exclusively down-regulated genes 1 h after GR-activation to both up and down regulated genes 3 h after GR-activation. After 5 h, the response was almost back to baseline. Additionally, real-time quantitative polymerase chain reaction was used for validation of a selection of responsive genes including genes involved in neurotransmission and synaptic plasticity such as the corticotropin releasing hormone receptor 1, monoamine oxidase A, LIMK1 and calmodulin 2. This permitted confirmation of GR-responsiveness of 15 out of 18 selected genes. In conclusion, direct activation of GR in hippocampal slices results in transient changes in gene expression. The pattern in which gene expression was modulated suggests that the fast genomic effects of glucocorticoids may be realised via transrepression, preceding a later wave of transactivation. Furthermore, we identified a number of interesting candidate genes which may underlie the glucocorticoid-mediated effects on hippocampal cell function. [source] Personality and Risk-Taking: Common Bisocial FactorsJOURNAL OF PERSONALITY, Issue 6 2000Marvin Zuckerman The first part of this article describes a study of the relationships between personality and risk-taking in six areas: smoking, drinking, drugs, sex, driving, and gambling. The participants, 260 college students, were given self-report measures of risky behaviors in each of the six areas and the Zuckerman- Kuhlman five-factor personality questionnaire. Generalized risk-taking (across all six areas) was related to scales for impulsive sensation seeking, aggression, and sociability, but not to scales for neuroticism or activity. Gender differences on risk-taking were mediated by differences on impulsive sensation seeking. The second part discusses biological traits associated with both risk-taking and personality, particularly sensation seeking, such as the D4 dopamine receptor gene, the enzyme monoamine oxidase, and augmenting or reducing of the cortical evoked potential. Comparative studies show relationships between biological markers shared with other species and correlated behaviors similar to sensation seeking in humans. A biosocial model of the traits underlying risk-taking is presented. [source] MAOA Interacts With the ALDH2 Gene in Anxiety,Depression Alcohol DependenceALCOHOLISM, Issue 7 2010Sheng-Yu Lee Background:, Alcohol dependence is usually comorbid with anxiety disorder, depressive disorder, or both; this comorbidity may increase drinking behavior. We previously hypothesized that anxiety,depressive alcohol dependence (ANX/DEP ALC) was a genetically specific subtype of alcohol dependence. ANX/DEP ALC may be related to dopamine and serotonin, which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The aim of this study was to determine whether the interaction between the MAOA and the ALDH2 genes is associated with ANX/DEP ALC. Methods:, We recruited 383 Han Chinese men in Taiwan: 143 ANX/DEP ALC and 240 healthy controls. The diagnosis of ANX/DEP ALC (alcohol dependence with a past or current history of anxiety, depressive disorder, or both) was made using DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR (variable number of tandem repeat located upstream) were determined using PCR-RFLP. Results:, The ALDH2, but not the MAOA-uVNTR, polymorphism was associated with ANX/DEP ALC. After stratifying the MAOA-uVNTR polymorphism, we found a stronger association between the ALDH2*1/*2 and *2/*2 genotypes and the controls in the MAOA-uVNTR 4-repeat subgroup. Logistic regression significantly associated the interaction between ALDH2 and MAOA variants with ANX/DEP ALC. Conclusion:, We conclude that the MAOA and ALDH2 genes interact in ANX/DEP ALC. Although the MAOA gene alone is not associated with ANX/DEP ALC, we hypothesize that different variants of MAOA-uVNTR polymorphisms modify the protective effects of the ALDH2*2 allele on ANX/DEP ALC in Han Chinese in Taiwan. [source] MAOA Alters the Effects of Heavy Drinking and Childhood Physical Abuse on Risk for Severe Impulsive Acts of Violence Among Alcoholic Violent OffendersALCOHOLISM, Issue 5 2010Roope Tikkanen Background:, A polymorphism in the promoter region of the monoamine oxidase A gene (MAOA) has been shown to alter the effect of persistent drinking and childhood maltreatment on the risk for violent and antisocial behaviors. These findings indicate that MAOA could contribute to inter-individual differences in stress resiliency. Methods:, Recidivism in severe violent crimes was assessed after 8 years of nonincarcerated follow-up in a male sample of 174 impulsive Finnish alcoholic violent offenders, the majority of whom exhibited antisocial (ASPD) or borderline personality disorder (BPD) or both. We examined whether MAOA genotype alters the effects of heavy drinking and childhood physical abuse (CPA) on the risk for committing impulsive recidivistic violent crimes. Results:, Logistic regression analyses showed that both heavy drinking and CPA were significant independent predictors of recidivism in violent behavior (OR 5.2, p = 0.004 and OR 5.3, p = 0.003) among offenders having the high MAOA activity genotype (MAOA-H), but these predictors showed no effect among offenders carrying the low MAOA activity genotype (MAOA-L). Conclusion:, Carriers of the MAOA-H allele have a high risk to commit severe recidivistic impulsive violent crimes after exposure to heavy drinking and CPA. [source] MAOA-uVNTR Polymorphism May Modify the Protective Effect of ALDH2 Gene Against Alcohol Dependence in Antisocial Personality DisorderALCOHOLISM, Issue 6 2009Sheng-Yu Lee Background:, Antisocial alcoholism is related to dopamine and serotonin which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The objective of this study is to determine whether the interaction between the MAOA and the ALDH2 genes is associated with subjects with antisocial personality disorder (ASPD) having alcoholism. Methods:, A total of 294 Han Chinese men in Taiwan including 132 ASPD with alcoholism (Antisocial ALC) and 162 without alcoholism (Antisocial Non-ALC) were recruited in this study. Alcohol dependence and ASPD were diagnosed according to DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR were determined using PCR-RFLP. Results:, A significant difference of ALDH2 polymorphisms (p = 3.39E-05), but not of MAOA, was found among the 2 study groups. However, only after the stratification of the MAOA-uVNTR (variable number of tandem repeat located upstream) 3-repeat, a significant association between Antisocial Non-ALC and ALDH2*1/*2 or *2/*2 genotypes was shown (p = 1.46E,05; odds ratio = 3.913); whereas stratification of MAOA-uVNTR 4-repeat revealed no association. Multiple logistic regression analysis further revealed significant interaction of MAOA and ALDH2 gene in antisocial ALC (odds ratio = 2.927; p = 0.032). Conclusion:, The possible interaction of MAOA and ALDH2 gene is associated with Antisocial ALC in Han Chinese males in Taiwan. However, the protective effects of the ALDH2*2 allele against alcoholism might disappear in subjects with ASPD and carrying MAOA-uVNTR 4-repeat allele in the Han Chinese male population. [source] Effects of MAOA -Genotype, Alcohol Consumption, and Aging on Violent BehaviorALCOHOLISM, Issue 3 2009Roope Tikkanen Background:, Environmental factors appear to interact with a functional polymorphism (MAOA-LPR) in the promoter region of the monoamine oxidase A gene (MAOA) in determining some forms of antisocial behavior. However, how MAOA - LPR modulates the effects of other factors such as alcohol consumption related to antisocial behavior is not completely understood. Methods:, This study examines the conjunct effect of MAOA-LPR, alcohol consumption, and aging on the risk for violent behavior. Recidivism in severe impulsive violent behavior was assessed after 7 to 15 years in a sample of 174 Finnish alcoholic offenders, the majority of whom exhibited antisocial or borderline personality disorder or both, and featured impulsive temperament traits. Results:, The risk for committing new acts of violence increased by 2.3% for each kilogram of increase in yearly mean alcohol consumption (p = 0.004) and decreased by 7.3% for every year among offenders carrying the high activity MAOA genotype. In contrast, alcohol consumption and aging failed to affect violent behavior in the low activity MAOA genotyped offenders. MAOA-LPR showed no main effect on the risk for recidivistic violence. Conclusions:, Violent offenders carrying the high activity MAOA genotype differ in several ways from carriers with the low activity MAOA risk allele previously associated with antisocial behavior. Finnish high activity MAOA genotyped risk alcoholics exhibiting antisocial behavior, high alcohol consumption, and abnormal alcohol-related impulsive and uncontrolled violence might represent an etiologically distinct alcohol dependence subtype. [source] Genetic polymorphism as a background of animal behaviorANIMAL SCIENCE JOURNAL, Issue 2 2009Miho INOUE-MURAYAMA ABSTRACT Various studies have shown the associations between differences in human behavioral traits and genetic polymorphism of neurotransmitter-related proteins such as receptors, transporters and monoamine oxidase. To clarify the genetic background of animal behavior, corresponding regions in animals have been analyzed. The study has been especially focused on primates, as the evolutionally closest animal to humans, and on dogs, as the socially closest animal to humans. In primates, polymorphisms were discovered between or within species, and the functional effects on neural transmission were found to be different by alleles. Even in apes, the closest species to humans, function was different from that in humans. In dogs, allele distributions of several genes were different among breeds showing different behavioral traits, and genes associated with individual differences in aggressiveness and aptitude of working dogs were surveyed. The survey of behavior-related genes has also been carried out in other mammals such as horses and cetaceans. Genes controlling various behaviors in birds have also been reported. The marker genes for behavior will provide useful information for human evolution, welfare of zoo animals and effective selection of working dogs and industry animals. [source] Promoting effect and recovery activity from physical stress of the fruit of Morus albaBIOFACTORS, Issue 1-4 2004Keum 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] Calcitonin gene-related peptide facilitates serotonin release from guinea-pig colonic mucosa via myenteric neurons and tachykinin NK2/NK3 receptorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2004Shu-ichi Kojima The ability of calcitonin gene-related peptide (CGRP), to alter the outflow of 5-hydroxytryptamine (5-HT) from the guinea-pig proximal colon, was evaluated using three different isolated preparations: whole colon, mucosa-free muscle layer and submucosa/mucosa preparations. In the presence of the monoamine oxidase A inhibitor, clorgyline, CGRP elicited a concentration-dependent increase in 5-HT outflow from the whole colon, but not from mucosa-free muscle layer preparations. The CGRP-evoked 5-HT outflow was sensitive to tetrodotoxin (TTX) or hexamethonium, but was not detectable in submucosa/mucosa preparations. HCGRP8,37 (3 ,M) inhibited the submaximal effect of CGRP on the 5-HT outflow. [Cys(ACM)2,7]hCGRP had a slight stimulant influence on the 5-HT outflow. The selective NK2 and NK3 receptor antagonists, SR48968 or SR142801, respectively, prevented the enhancing effect of CGRP. By contrast, a selective NK1 receptor antagonist L703606, failed to block the effect of CGRP. The enhancing effect of CGRP was mimicked by the NK2 receptor agonist [, -Ala8]-neurokinin A (NKA)4,10 and the NK3 receptor agonist senktide. The effect of [, -Ala8]-NKA4,10 on the 5-HT outflow was unaffected by TTX, while the effect of senktide was prevented by TTX, hexamethonium or SR48968. The present data also demonstrated a synergistic action of the NK2 and NK3 receptor agonists on the CGRP-evoked 5-HT outflow. We concluded that CGRP facilitates 5-HT release from the guinea-pig colonic mucosa through an action on myenteric neurons and that this effect is mediated by endogenously released tachykinins, acting via tachykinin NK2/NK3 receptors in cascade. British Journal of Pharmacology (2004) 141, 385,390. doi:10.1038/sj.bjp.0705624 [source] The genetics of panic disorder: state of the artACTA NEUROPSYCHIATRICA, Issue 2 2004Dirk Van West Panic disorder (PD) is a highly prevalent, debilitating disorder. The heritability of the disease has been estimated by twin studies to be between 30 and 60%. The vulnerability for PD overlaps with an increased risk of bipolar disorder in some families. Classical genetic methods such as linkage analysis and association studies have not yet identified genetic risk factors beyond doubt. However, two independent studies confirm linkage of a specific syndrome characterized by PD, bladder problems, severe headaches, mitral valve prolapse and thyroid dysfunction to genetic markers on chromosome 13q. Association studies, although showing divergent results, give some support to a causative role for the genes encoding for monoamine oxidase A (MAO-A), cholecystokinin (CCK) and catechol-O-methyltransferase (COMT). Finally, a somatic duplication of a 19-Mb region on chromosome 15 has been associated with PD, but this intriguing finding awaits confirmation. [source] Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymesCHIRALITY, Issue 3 2005Wataru Takasaki Abstract RS-8359, (±)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H -cyclopenta[d]pyrimidine selectively and reversibly inhibits monoamine oxidase A (MAO-A). After oral administration of rac -RS-8359 to rats, mice, dogs, monkeys, and humans, plasma concentrations of the (R)-enantiomer were greatly higher than were those of the (S)-enantiomer in all species studied. The AUC(R) to AUC(S) ratios were 2.6 in rats, 3.8 in mice, 31 in dogs, and 238 in monkeys, and the (S)-enantiomer was almost negligible in human plasma. After intravenous administration of RS-8359 enantiomers to rats, the pharmacokinetic parameters showed that the (S)-enantiomer had a 2.7-fold greater total clearance (CLt) and a 70% shorter half-life (t1/2) than those for the (R)-enantiomer but had no difference in distribution volume (Vd). No significant difference in the intestinal absorption rate was observed. The principal metabolites were the 2-keto form, possibly produced by aldehyde oxidase, the cis -diol form, and the 2-keto- cis -diol form produced by cytochrome P450 in rats, the cis -diol form in mice, RS-8359 glucuronide in dogs, and the 2-keto form in monkeys and humans. Thus, the rapid disappearance of the (S)-enantiomer from the plasma was thought to be due to the rapid metabolism of the (S)-enantiomer by different drug-metabolizing enzymes, depending on species. Chirality 17:135,141, 2005. © 2005 Wiley-Liss, Inc. [source] Biotransformation of xenobiotics by amine oxidasesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2001Margherita Strolin Benedetti Although the cytochrome P450 (CYP) system ranks first in terms of catalytic versatility and the wide range of xenobiotics it detoxifies or activates to reactive intermediates, the contribution of amine oxidases and in particular of monoamine oxidases (MAOs) to the metabolism of xenobiotics is far from negligible but has been largely neglected. In this review on the involvement of amine oxidases in the metabolism of xenobiotics, the major characteristics reported for the CYP system (protein, reaction, tissue distribution, subcellular localisation, substrates, inhibitors, inducers, genetic polymorphism, impact of different physiopathological conditions on the activity, turnover) will be compared, whenever possible, with the corresponding characteristics of amine oxidases (MAOs in particular). The knowledge of the involvement of MAO-A, -B or both in the metabolism of a drug allows us to predict interactions with selective or non-selective MAO inhibitors (e.g. the metabolism of a drug deaminated by both forms of MAO is not necessarily inhibited in vivo by a selective MAO-A or -B inhibitor). If a drug is metabolized by MAOs, competitive interactions can occur with other drugs that are MAO substrates, e.g. with ,-adrenoceptor agonists and antagonists, prodrugs of dopamine, serotonin 5-HT1 -receptor agonists as well as with primaquine, flurazepam and citalopram. Moreover, the knowledge of the involvement of MAOs in the metabolism of a drug may suggest possible, although not obligatory, interactions with tyramine-containing food or drink, with over the counter medicines sold to relieve the symptoms of coughs and colds (generally containing the indirectly-acting sympathomimetic amine phenylpropanolamine) or with phenylephrine-containing preparations. Finally, biotransformation by amine oxidases, as by CYP, does not always lead to detoxication but can produce toxic compounds. [source] Structure,Activity Relationships of SSAO/VAP-1 Arylalkylamine-Based SubstratesCHEMMEDCHEM, Issue 4 2009Francesc Yraola Dr. Abstract SSAO/VAP-1 substrates may be valuable for the treatment or prevention of diabetes mellitus, as they show insulin-mimetic properties. This review highlights the importance of studying the relevant steric and electronic features in the development of new ligands with better SSAO/VAP-1 recognition, enhanced selectivity over other amine oxidases, and improved metabolic behavior. Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) substrates show insulin-mimetic effects and are therefore potentially valuable molecules for the treatment of diabetes mellitus. Herein we review several structural and electronic aspects of SSAO arylalkylamine-based substrates. Two main modifications directly affect amine oxidase (AO) activity: 1),variation in ring substitution modulates the biological activity of the arylalkylamine ligand by converting a substrate into a substrate-like inhibitor, and 2),variation in the number of methylene units between the aromatic ring and the ammonium groups of the arylalkylamine substrates dramatically alters the oxidation rate between species. Furthermore, we review relevant information about mammalian SSAO/VAP-1 substrate selectivity and specificity over monoamine oxidases (MAOs). [source] | |||||||||||||||||||||||||||||||