monoamine oxidase A/B Dotaz Zobrazit nápovědu
Monoaminooxidáza B (MAO-B) je enzym, který se účastní metabolismu dopaminu, benzylaminu, fenylethylaminu, tyraminu a tryptaminu. Aktivita enzymu MAO-B byla již vícekrát asociována s některými psychickými poruchami, mimo jiné i s afektivními poruchami. Polymorfismus A/G v intronu 13. genu pro MAO-B ovlivňuje variabilitu aktivity enzymu MAO-B. Cílem této studie bylo zjistit, zda existuje vztah mezi tímto polymorfismem genu pro MAO-B a intenzitou pooperační bolesti. Testovali jsme celkem 284 osob (105 mužů a 179 žen), které se podrobily plánované tonzilektomii. Pro detekci polymorfismu byla použita metoda řetězové polymerázové reakce (PCR) s alelově specifickými primery. Bolest byla měřena pomocí vizuální analogové škály VAS. V naší práci jsme ve skupině mužů objevili vztah mezi polymorfismem A/G v intronu 13 genu pro MAO-B a průměrnou intenzitou pooperační bolesti. Zjistili jsme statisticky významně vyšší průměrnou intenzitu pooperační bolesti u mužů s alelou G ve srovnání s muži s alelou A. Výsledky naší studie naznačují vztah mezi polymorfismem genu pro MAO-B a průměrnou intenzitou pooperační bolesti u mužů České republiky. Možná role MAO-B ve vnímání intenzity bolesti je diskutována především v souvislosti s vlivem MAO-B na psychickou náladu.
The monoamine oxidase B (MAO-B) is an enzyme involved in the metabolism of dopamine, benzylamine, phenylethylamine, tyramine and tryptamine. MAO-B activity was associated many times with some psychiatric diseases including affective disorders. The A/G polymorphism in intron 13 of the MAO-B gene was previously associated with a variability of the MAO-B enzyme activity. The aim of the present association study was to examine the relationship between the A/G polymorphism in intron 13 and postoperative pain intensity. We examined 284 subjects (105 males and 179 females) that underwent planned tonsillectomy. PCR method with allele specific primers for the detection of A/G polymorphism was used. The intensity of pain was tested by visual analogue scale (VAS). We found a relationship between the A/G polymorphism in intron 13 of the MAO-B gene and average intensity of postoperative pain in male subjects. We found statistically significantly higher average intensity of postoperative pain in males with G allele in comparison with males with A allele. Results of our study indicate the relationship between the MAO-B polymorphism and postoperative pain intensity in Czech male population. The potential role of the MAO-B in feeling of pain intensity is discussed mainly in the context of the influence of MAO-B on the mood.
- MeSH
- DNA genetika MeSH
- estrogeny krev MeSH
- finanční podpora výzkumu jako téma MeSH
- genotyp MeSH
- lidé MeSH
- měření bolesti metody MeSH
- monoaminoxidasa fyziologie genetika krev MeSH
- polymorfismus genetický MeSH
- pooperační bolest etiologie farmakoterapie genetika MeSH
- tonzilektomie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
Pharmacology and toxicology, ISSN 0901-9936 vol. 60, suppl. I, 1987
56, x s. ; 26 cm
- MeSH
- benzylaminoxidasa MeSH
- biochemie MeSH
- farmakologie MeSH
- monoaminoxidasa MeSH
- Publikační typ
- kongresy MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmacie a farmakologie
- toxikologie
- biochemie
Acta psychiatrica Scandinavica ; Supplement Vol. 91. 386
43 s. : tab. ; 28 cm
- MeSH
- aminy metabolismus MeSH
- deprese farmakoterapie MeSH
- inhibitory MAO farmakologie MeSH
- noradrenalin fyziologie MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- psychofarmakologie
- psychiatrie
- behaviorální vědy
Progress in understanding the role of monoamine neurotransmission in pathophysiology of neuropsychiatric disorders was made after the discovery of the mechanisms of action of psychoactive drugs, including monoamine oxidase (MAO) inhibitors. The increase in monoamine neurotransmitter availability, decrease in hydrogen peroxide production, and neuroprotective effects evoked by MAO inhibitors represent an important approach in the development of new drugs for the treatment of mental disorders and neurodegenerative diseases. New drugs are synthesized by acting as multitarget-directed ligands, with MAO, acetylcholinesterase, and iron chelation as targets. Basic information is summarized in this paper about the drug-induced regulation of monoaminergic systems in the brain, with a focus on MAO inhibition. Desirable effects of MAO inhibition include increased availability of monoamine neurotransmitters, decreased oxidative stress, decreased formation of neurotoxins, induction of pro-survival genes and antiapoptotic factors, and improved mitochondrial functions.
- MeSH
- duševní poruchy farmakoterapie enzymologie MeSH
- inhibitory MAO chemická syntéza farmakologie terapeutické užití MeSH
- lidé MeSH
- monoaminoxidasa metabolismus MeSH
- nervový přenos účinky léků fyziologie MeSH
- neurodegenerativní nemoci farmakoterapie enzymologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and psychotropic drugs, including cannabinoids. This study investigated in vitro effects of cannabinoids on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters and affecting brain development and function. The effects of the phytocannabinoid Delta(9)-tetrahydrocannabinol (THC), the endocannabinoid anandamide (N-arachidonoylethanolamide [AEA]), and the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) on the activity of MAO were measured in a crude mitochondrial fraction isolated from pig brain cortex. Monoamine oxidase activity was inhibited by the cannabinoids; however, higher half maximal inhibitory concentrations (IC(50)) of cannabinoids were required compared to the known MAO inhibitor iproniazid. The IC(50) was 24.7 micromol/l for THC, 751 micromol/l for AEA, and 17.9 micromol/l for WIN when serotonin was used as substrate (MAO-A), and 22.6 micromol/l for THC, 1,668 micromol/l for AEA, and 21.2 micromol/l for WIN when phenylethylamine was used as substrate (MAO-B). The inhibition of MAOs by THC was noncompetitive. N-Arachidonoylethanolamide was a competitive inhibitor of MAO-A and a noncompetitive inhibitor of MAO-B. WIN was a noncompetitive inhibitor of MAO-A and an uncompetitive inhibitor of MAO-B. Monoamine oxidase activity is affected by cannabinoids at relatively high drug concentrations, and this effect is inhibitory. Decrease of MAO activity may play a role in some effects of cannabinoids on serotonergic, noradrenergic, and dopaminergic neurotransmission.
- MeSH
- benzoxaziny aplikace a dávkování farmakologie MeSH
- inhibiční koncentrace 50 MeSH
- inhibitory MAO aplikace a dávkování farmakologie MeSH
- iproniazid aplikace a dávkování farmakologie MeSH
- kyseliny arachidonové aplikace a dávkování farmakologie MeSH
- monoaminoxidasa účinky léků metabolismus MeSH
- morfoliny aplikace a dávkování farmakologie MeSH
- mozek účinky léků enzymologie MeSH
- naftaleny aplikace a dávkování farmakologie MeSH
- polynenasycené alkamidy aplikace a dávkování farmakologie MeSH
- prasata MeSH
- tetrahydrokanabinol aplikace a dávkování farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Progress in understanding the mechanisms of action of cannabinoids was made after discovery of cannabinoid receptors and finding their endogenous ligands. New findings are obtained using both endogenous cannabinoids and plant or synthetic cannabinoids. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neuromodulation of synapses by cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some neurodegenerative and mental disorders. Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and by different psychotropic drugs, including cannabinoids. Basic information is summarized in the paper about mechanisms of action of cannabinoids on monoaminergic systems, with a view to inhibition of monoamine oxidase.
- MeSH
- biogenní monoaminy metabolismus MeSH
- duševní poruchy metabolismus MeSH
- kanabinoidy metabolismus MeSH
- monoaminoxidasa metabolismus MeSH
- mozek metabolismus MeSH
- nervový přenos fyziologie MeSH
- neuroplasticita fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Administration of acetylcholinesterase (AChE) reactivators (oximes) is usually used in order to counteract the poisoning effects of nerve agents. The possibility was suggested that oximes may show some therapeutic and/or adverse effects through their action in central nervous system. There are no sufficient data about interaction of oximes with monoaminergic neurotransmitter's systems in the brain. Oxime-type AChE reactivators pralidoxime, obidoxime, trimedoxime, methoxime and HI-6 were tested for their potential to affect the activity of monoamine oxidase of type A (MAO-A) and type B (MAO-B) in crude mitochondrial fraction of pig brains. The compounds were found to inhibit fully MAO-A with half maximal inhibitory concentration (IC(50)) of 0.375 mmol/l (pralidoxime), 1.53 mmol/l (HI-6), 2.31 mmol/l (methoxime), 2.42 mmol/l (obidoxime) and 4.98 mmol/l (trimedoxime). Activity of MAO-B was fully inhibited by HI-6 and pralidoxime only with IC(50) 4.81 mmol/l and 11.01 mmol/l, respectively. Methoxime, obidoxime and trimedoxime displayed non-monotonic concentration dependent effect on MAO-B activity. Because oximes concentrations effective for MAO inhibition could not be achieved in vivo at the cerebral level, we suppose that oximes investigated do not interfere with brain MAO at therapeutically relevant concentrations.
- MeSH
- inhibitory MAO farmakologie MeSH
- monoaminoxidasa metabolismus MeSH
- mozek enzymologie MeSH
- obidoxim chlorid farmakologie MeSH
- oximy farmakologie MeSH
- pralidoximové sloučeniny farmakologie MeSH
- prasata MeSH
- pyridinové sloučeniny farmakologie MeSH
- reaktivátory cholinesterázy farmakologie MeSH
- trimedoxim farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lidské monoaminooxidasy (hMAOs) jsou mitochondriální enzymy katalyzující degradaci biogenních aminů. Téměř ve všech tkáních nalézáme dvě isoformy – hMAO A a hMAO B. Inhibitory hMAO A patří mezi dlouhodobě nejpoužívanější antidepresiva. Díky strukturním studiím, které odhalily rozdíly mezi oběma isoformami, mohou být efektivně navrhovány velmi specifické reversibilní inhibitory. Možnost použití inhibitorů zacílených pouze proti jednomu z enzymů významně zlepšuje jejich terapeutický potenciál. Dnes se inhibitory hMAO B standardně používají k léčbě Parkinsonovy choroby a další možnosti aplikací jsou ve fázi klinického testování. Tento článek shrnuje základní problematiku hMAOs a jejich inhibitorů.
Human monoamine oxidases (hMAOs) are mitochondrial enzymes that catalyze degradation of biogenic amines. In almost all tissues are found two isoforms – hMAO A and hMAO B. Inhibitors of hMAO A belongs to one of the longest used antidepressants. Specific reversible inhibitors could be effectively designed due to structural studies that reveal differences between both isoforms. The possibility of application of inhibitors targeting only one of the enzymes significantly improves their therapeutic potential. hMAO B inhibitors are currently commonly used to treat Parkinson’s disease. Other applications of hMAO B inhibitorsare in the clinical trial phase. This article summarizes basic issues of hMAOs and their inhibitors.
