• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• psychofarmakologie

• 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

• MeSH
• inhibitory MAO farmakokinetika   farmakologie   terapeutické užití   MeSH
• management farmakoterapie MeSH
• Parkinsonova nemoc farmakoterapie   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie

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

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.

• MeSH
• inhibitory MAO * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• monoaminoxidasa * fyziologie   metabolismus   MeSH
• neurodegenerativní nemoci farmakoterapie   MeSH
• Parkinsonova nemoc farmakoterapie   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• deprese - farmakoterapie - sborníky prací, antidepresiva - užití - účinky - sborníky prací, inhibitory monoaminoxydázy - užití - účinky - sborníky prací,

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• farmacie a farmakologie
• biochemie

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

• MeSH
• inhibitory MAO MeSH
• játra MeSH
• kyseliny indoloctové MeSH
• mozek MeSH
• serotonin MeSH

ETHNOPHARMACOLOGICAL RELEVANCE: The development of selective inhibitors of monoamine oxidase B (MAO-B) has been essential in treating Parkinson's disease. However, the apparent hepatotoxicity and drug-drug interactions of current inhibitors accentuate the need for the development of novel pharmacotherapies. Crossyne guttata (L.) D. & U. Müll-Doblies is used frequently by Rastafarian bush doctors to treat alcoholism, a disorder which is also accentuated by MAO. OBJECTIVE: The study sought to isolate, identify and characterise the biologically active constituents of C. guttata based on their ability to inhibit the MAO enzymes. MATERIALS AND METHODS: Column chromatography was used to isolate the biologically active alkaloids of C. guttata. The ability of the alkaloids to inhibit the biotransformation of 4-aminoantipyrine by the MAO enzymes was evaluated in vitro. In silico docking was conducted using AutoDock Vina server while the pharmacokinetic properties of the compounds were evaluated using SwissADME. RESULTS: Chromatographic separation of an ethanolic fraction of C. guttata yielded the alkaloids crinamine 1 and epibuphanisine 2. 1 and 2 along with structurally related alkaloids haemanthamine 3 and haemanthidine 4 were evaluated for their ability to inhibit the action of isozymes of MAO in vitro. Alkaloids effected submicromolar IC50 values against MAO-B, the most potent of which being crinamine 1 (0.014 μM) > haemanthidine 4 (0.017 μM) > epibuphanisine 2 (0.039 μM) > haemanthamine 3 (0.112 μM). Binding energies of the alkaloids correlated well with their inhibitory potential with crinamine displaying the best binding efficacy and binding energy score with MAO-B. DISCUSSION AND CONCLUSION: Crinamine and epibuphanisine exhibited potent and selective inhibitory activity towards MAO-B. After comprehensive in silico investigations encompassing robust molecular docking analysis, the drug-like attributes and safety of the alkaloids suggest the crinamine is a potentially safe drug for human application.

• MeSH
• alkaloidy amarylkovitých chemie   farmakokinetika   farmakologie   toxicita   MeSH
• bezpečnost pacientů MeSH
• biologické modely * MeSH
• Cercopithecus aethiops MeSH
• hodnocení rizik MeSH
• inhibitory MAO chemie   farmakokinetika   farmakologie   toxicita   MeSH
• konformace proteinů MeSH
• lidé MeSH
• monoaminoxidasa chemie   metabolismus   MeSH
• mutace MeSH
• Salmonella typhimurium účinky léků   genetika   MeSH
• simulace molekulového dockingu * MeSH
• Vero buňky MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH