Patocka J


Full name : Patocka Jiri

First name : Jiri

Mail : University Hospital Hradec Kralove

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Country : Czech Republic

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References (44)

Title : Novichok agents -mysterious poisonous substances from the cold war period - Patocka_2018_Mil.Med.Sci.Lett_87_1
Author(s) : Patocka J
Ref : Military Medical Science Letters , 87 :1 , 2018
Abstract : On March 4, Sergei Skripal, a former Russian spy who was convicted and imprisoned in Russia for working as a double agent, and his daughter were found unresponsive and slumped on a shopping-center bench in Salisbury, England. On 12 March 2018, British Prime Minister Theresa May said in Parliament that the two had been poisoned with Novichok, a 'military grade' nerve agent developed by Russia, and she moved swiftly to retaliate against the government of President Vladimir Putin (BBC News, 12 March 2018). It was the first use of a nerve agent on European soil since World War II. Russian authorities have rejected May's claims as nonsense. On 14 March 2018, the UK expelled 23 Russian diplomats after the Russian government refused to meet the UK's deadline of midnight on 13 March 2018 to give an explanation for the use of the substance (BBC News, 14 March 2018). The whole world has learned about the existence of a highly toxic neuro-paralytic substance called Novichok, which should have been destroyed under the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction ( It will not hurt to tell what's behind Novichok, what substances are involved and how dangerous they are. Novichok is a series of nerve agents the Soviet Union and Russia developed between 1971-1993 (Tucker, 2006; Ellison, 2007). They were designed as part of a Soviet program codenamed "FOLIANT" (Pitschmann, 2014), nevertheless Russia officially denies producing or researching Novichok agents (Borger, 2018). Novichok agents were developed during the Cold War period and have never been used on the battlefield. In 2011, the Organisation for the Prohibition of Chemical Weapons (OPCW) Scientific Advisory Board reported that no peer reviewed paper on Novichok agents in scientific literature exist (OPCW Report, 2011) and in 2013 OPCW reported that it had insufficient information to comment on the existence or properties of Novichok agents (OPCW Report, 2013). Since then, new information has emerged that confirms the existence of Novichok agents and brings more information about them. Novichok agents are binary weapons, in which precursors for the nerve agents are mixed in a munition to produce the agent just prior to its use (Darling and Noste, 2016). Because the precursors are generally significantly less hazardous than the agents themselves, this technique makes handling and transporting the munitions a great deal simpler. Additionally, precursors to the agents are usually much easier to stabilize than the agents themselves, so this technique also made it possible to increase the shelf life of the agents. Binary weapons are safer to store, transport and handle. Different dihalonitrosomethanes or nitromethanes serves as precursors of Novichok agents. These react with phosphorus halides, phosphite, phosphate and alkylphosphonate esters to form formaldoximes. Novichok family of analogs comprises more than a hundred structural variants. From a military standpoint, the most pronounced Novichok was A-232 (Novichok-5). Other possible organophosphate molecules that can be ranked among Novichok agents are shown
ESTHER : Patocka_2018_Mil.Med.Sci.Lett_87_1
PubMedSearch : Patocka_2018_Mil.Med.Sci.Lett_87_1

Title : A Resurrection of 7-MEOTA: A Comparison with Tacrine - Soukup_2013_Curr.Alzheimer.Res_10_893
Author(s) : Soukup O , Jun D , Karasova JZ , Patocka J , Musilek K , Korabecny J , Krusek J , Kaniakova M , Sepsova V , Mandikova J , Trejtnar F , Pohanka M , Drtinova L , Pavlik M , Tobin G , Kuca K
Ref : Curr Alzheimer Res , 10 :893 , 2013
Abstract : Alzheimer s disease (AD) is a progressive neurodegenerative dementia which currently represents one of the biggest threats for the human kind. The cure is still unknown and various hypotheses (cholinergic, amyloidal, oxidative, vascular etc.) are investigated in order to understand the pathophysiology of the disease and on this basis find an effective treatment. Tacrine, the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug, however it was withdrawn from the market particularly due to its hepatotoxicity. Its derivative 7-methoxytacrine (7- MEOTA) probably due to the different metabolization does not exert this side effect. The aim of our study was to compare these two cholinesterase inhibitors from various, mainly cholinergic, points of view relevant for a potential AD drug. We found that 7-MEOTA does not fall behind its more well-known parent compound - tacrine. Furthermore, we found, that 7-MEOTA exerts better properties in most of the tests related to a possible AD treatment. Only the pharmacokinetics and a higher acetylcholinesterase and butyrylcholinesterase inhibitory potency would slightly give advantages to tacrine over 7-MEOTA, but concerning its lower toxicity, better antioxidant properties, interaction with muscarinic and nicotinic receptors and "safer" metabolization provide strong evidence for reconsider 7-MEOTA and its derivatives as candidate molecules for the treatment of AD.
ESTHER : Soukup_2013_Curr.Alzheimer.Res_10_893
PubMedSearch : Soukup_2013_Curr.Alzheimer.Res_10_893
PubMedID: 24093535

Title : Anatoxin-a(s): natural organophosphorus anticholinesterase agent - Patocka_2011_Mil.Med.Sci.Lett_80_129
Author(s) : Patocka J , Gupta RC , Kuca K
Ref : Military Medical Science Letters , 80 :129 , 2011
Abstract : Anatoxin-a(s) is a guanidinemethyl phosphate ester isolated from the freshwater cyanobacterium (blue-green algae) Anabaena flos-aquae strain NRC 525-17. Previous work has shown anatoxin-a(s) to be a potent irreversible inhibitor of electric eel acetylcholinesterase (AChE, EC Anatoxin-a(s) has been shown to be an active site-directed inhibitor of AChE, which is resistant to reactivation by oximes because of the enzyme-oxime adduct formation. In vivo pretreatment with physostigmine and high concentrations of pyridine 2-aldoxime methochloride (2-PAM) were the only effective antagonists against a lethal dose of anatoxin-a(s). Anatoxin-a(s) is very toxic and it is produced by cyanobacteria during its blooms. Purified toxin has an LD50 (i.p) of approximately 20-50 g/kg body weight in mice. Toxicoses associated with cholinesterase-inhibiting anatoxin-a(s) have been observed in humans, animals, birds and fish. Anatoxin-a(s) induces clinical signs of hypercholinergic preponderance, such as salivation, lacrimation, urinary incontinence, defecation, convulsion, fasciculation, and respiratory arrest.
ESTHER : Patocka_2011_Mil.Med.Sci.Lett_80_129
PubMedSearch : Patocka_2011_Mil.Med.Sci.Lett_80_129

Title : Novel acetylcholinesterase reactivator K112 and its cholinergic properties - Soukup_2010_Biomed.Pharmacother_64_541
Author(s) : Soukup O , Kristofikova Z , Proska J , Tobin G , Patocka J , Marek J , Jun D , Fusek J , Ripova D , Kuca K
Ref : Biomed Pharmacother , 64 :541 , 2010
Abstract : The oxime reactivator K112 is a member of the new group of xylene linker-containing AChE reactivators. Its cholinergic properties could be of importance at OP poisoning and are not related to the AChE reactivation that has been studied. It has been found that, despite of reactivating potency, this compound has additional effects. These cholinergic effects include a weak inhibition of AChE (IC(50)=43.8 +/- 4.88 muM), inhibition of binding to the porcine muscarinic M2 receptor (IC(50)=4.36 muM) and finally, the inhibition of HACU (68.4 +/- 9.9%), a key regulatory step in the synthesis of ACh. The inhibition of the binding of (3H)-HC-3 (64.7 +/- 4.7%) and the influence on the membrane fluidity have also been observed. Blocking properties of K112 on the muscarinic receptors have been revealed in the in vitro experiment (rat urinary bladder) and in the in vivo experiment (rat heart BPM) as well. All these cholinergic properties could significantly contribute to the antidotal effect of K112 at the poisoning by the organophosphates.
ESTHER : Soukup_2010_Biomed.Pharmacother_64_541
PubMedSearch : Soukup_2010_Biomed.Pharmacother_64_541
PubMedID: 20634031

Title : Who Synthetised the First Organophosphorus Inhibitor of Acetylcholinesterase? - Patocka_2010_Mil.Med.Sci.Lett_79_126
Author(s) : Patocka J
Ref : Military Medical Science Letters , 79 :126 , 2010
Abstract : The tetraethyl pyrophosphate (TEPP), the first synthetically prepared organophosphorus inhibitor of acetylcholinesterase, is put down to the French chemist Philippe de Clermont. Nevertheless, certain facts show that the first synthesis of TEPP was achieved by Clermont's colleague, likewise working in Adolphe Wurtz's laboratory in Paris. This person was a Russian student, Wladimir Petrovich Moschnine from Moscow. While Clermont was well known, nobody knew who Moschnine was. Due to young Portuguese researcher, Ana Carneiro, and Professor George A. Petroianu from the United Arab Emirates University, they managed to elucidated yet unknown history of organophosphate cholinesterase inhibitors.
ESTHER : Patocka_2010_Mil.Med.Sci.Lett_79_126
PubMedSearch : Patocka_2010_Mil.Med.Sci.Lett_79_126

Title : Synthesis and in vitro evaluation of N-(Bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer's disease treatment - Korabecny_2010_Molecules_15_8804
Author(s) : Korabecny J , Musilek K , Holas O , Nepovimova E , Jun D , Zemek F , Opletalova V , Patocka J , Dohnal V , Nachon F , Hroudova J , Fisar Z , Kuca K
Ref : Molecules , 15 :8804 , 2010
Abstract : A new tacrine based cholinesterase inhibitor, N-(bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine (1), was designed and synthesized to interact with specific regions of human acetylcholinesterase and human butyrylcholinesterase. Its inhibitory ability towards cholinesterases was determined and compared to tacrine (THA) and 9-amino-7-methoxy-1,2,3,4-tetrahydroacridine (7-MEOTA). The assessment of IC50 values revealed 1 as a weak inhibitor of both tested enzymes.
ESTHER : Korabecny_2010_Molecules_15_8804
PubMedSearch : Korabecny_2010_Molecules_15_8804
PubMedID: 21127466

Title : Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer's disease - Patocka_2008_Curr.Drug.Metab_9_332
Author(s) : Patocka J , Jun D , Kuca K
Ref : Curr Drug Metab , 9 :332 , 2008
Abstract : Tacrine belongs to the group of acetylcholinesterse (AChE) inhibitors used as drugs for treatment of Alzheimer's disease (AD). The formation of hydroxyderivatives of tacrine is well-established step in the metabolization of this drug in liver by microsomal cytochrome P450 enzymes family. Genetic polymorphism of cytochrome P450 enzymes is probably responsible for balance between a number of stable and non-toxic metabolites and highly protein-reactive and toxic ones. By this manner may be explained why the hepatotoxicity of tacrine was observed only in the part of persons and why not every patient with AD responds to the treatment by this drug.
ESTHER : Patocka_2008_Curr.Drug.Metab_9_332
PubMedSearch : Patocka_2008_Curr.Drug.Metab_9_332
PubMedID: 18473751

Title : Tests with Daphnia magna: a new approach to prescreen toxicity of newly synthesized acetylcholinesterase reactivators - Vesela_2006_J.Enzyme.Inhib.Med.Chem_21_427
Author(s) : Vesela S , Ondruska V , Kuca K , Patocka J
Ref : J Enzyme Inhib Med Chem , 21 :427 , 2006
Abstract : Reactivators of phosphorylated acetylcholinesterase (oximes) are substances used as a human antidotal therapy for organophosphate poisoning. The objective of our study was to examine if juveniles of freshwater microcrustacean Daphnia magna could be employed as test animals in early screen toxicity tests of those substances as a first step for further experiments with daphnids intoxicated by organophosphates. For this purpose, seven different oximes were investigated. It was found that toxicity of all tested oximes increased with time. Mono-quaternary oximes were approximately ten fold (EC50, 14.9 mg.l(-1)) more toxic in 24 hour tests and five fold (EC50 was 79.46 mg.l(-1)) more toxic in 48 hour tests than bis-quaternary oximes. Tests with daphnids were shown to be easy to carry out at low cost and provided valuable results which could be used as a starting point for further research.
ESTHER : Vesela_2006_J.Enzyme.Inhib.Med.Chem_21_427
PubMedSearch : Vesela_2006_J.Enzyme.Inhib.Med.Chem_21_427
PubMedID: 17059176
Gene_locus related to this paper: dapul-ACHE1

Title : New quaternary pyridine aldoximes as casual antidotes against nerve agents intoxications - Kuca_2005_Biomed.Pap.Med.Fac.Univ.Palacky.Olomouc.Czech.Repub_149_75
Author(s) : Kuca K , Bartosova L , Jun D , Patocka J , Cabal J , Kassa J , Kunesova G
Ref : Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub , 149 :75 , 2005
Abstract : In this work, the ability of four newly synthesized oximes--K005 (1,3-bis(2-hydroxyiminomethylpyridinium) propane dibromide), K027 (1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide), K033 (1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide) and K048 (1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide) to reactivate acetylcholinesterase (AChE, EC inhibited by nerve agents is summarized. Reactivation potency of these compounds was tested using standard in vitro reactivation test. Tabun, sarin, cyclosarin and VX agent were used as appropriate testing nerve agents. Rat brain AChE was used as a source of the enzyme. Efficacies of new reactivators to reactivate tabun-, sarin-, cyclosarin- and VX-inhibited AChE were compared with the currently used AChE reactivators (pralidoxime, obidoxime and HI-6). Oxime K048 seems to be promising reactivator of tabun-inhibited AChE. Its reactivation potency is significantly higher than that of HI-6 and pralidoxime and comparable with the potency of obidoxime. The best reactivator of sarin-inhibited AChE seems to be oxime HI-6. None of the new AChE reactivators reached comparable reactivation potency. The same results were obtained for cyclosarin-inhibited AChE. However, oxime K033 is also potent reactivator of AChE inhibited by this nerve agent. In the case of VX inhibition, obidoxime and new oximes K027 and K048 seem to be the best AChE reactivators. None from the currently tested AChE reactivators is able to reactivate AChE inhibited by all nerve agents used and, therefore, the search for new potential broad spectrum AChE reactivators is needed.
ESTHER : Kuca_2005_Biomed.Pap.Med.Fac.Univ.Palacky.Olomouc.Czech.Repub_149_75
PubMedSearch : Kuca_2005_Biomed.Pap.Med.Fac.Univ.Palacky.Olomouc.Czech.Repub_149_75
PubMedID: 16170392

Title : In vitro inactivation of rat brain acetylcholinesterase by DSP-4 and its derivatives OS-21 and OS-23 and protective activity of tacrine (9-amino-1,2,3,4-tetrahydroacridine) - Patocka_2005_Acta.Medica.(Hradec.Kralove)_48_145
Author(s) : Patocka J , Jun D , Kuca K
Ref : Acta Medica (Hradec Kralove) , 48 :145 , 2005
Abstract : Tertiary N-haloethylamines are able to cyclize to the corresponding aziridinium ions. The inhibitory activity of the DSP-4 (N-(o-brombenzyl)-N-ethyl-2-chlorethylamine) and its two derivatives OS-21 (N-benzyl-N-ethyl-2-chloroethylamine) and OS-23 (N-fenylethyl-N-ethyl-2-chloroethylamine) was studied toward rat brain acetylcholinesterase (AChE) in vitro. The influence of the THA (tacrine; 9-amino-1,2,3,4-tetrahydroacridine) on AChE inhibition by these substances was also evaluated. The results demonstrated that all of three aziridinium compounds formed in solution caused a time- and concentration-dependent irreversible enzyme inhibition. The association of aziridinium compounds with the AChE was a relatively slow second-order reaction. DSP-4 showed the fastest rate of AChE alkylation, OS-21 had a lowered rate and OS-23 displayed the lowest rate. Pretreatment of the enzyme by THA decreased the rate of alkylation by all three aziridinium compounds by allosteric mechanism.
ESTHER : Patocka_2005_Acta.Medica.(Hradec.Kralove)_48_145
PubMedSearch : Patocka_2005_Acta.Medica.(Hradec.Kralove)_48_145
PubMedID: 16640027

Title : Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes - Kuca_2004_Neurotox.Res_6_565
Author(s) : Kuca K , Patocka J , Cabal J , Jun D
Ref : Neurotox Res , 6 :565 , 2004
Abstract : We investigated the relationship between the chemical structure of acetylcholinesterase (AChE; EC reactivators and their potency in reactivating this enzyme, after prior inhibition by VX (O-ethyl-S-(2-diisopropylaminoethyl)-methylthiophosphonate), tabun, sarin, and cyclosarin. The oximes, pralidoxime (2-PAM), HI-6 [1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride], obidoxime and HS-6 [1-(2-hydroxyiminomethylpyridinium)-3-(3-carbamoylpyridinium)-2-oxa-propane dichloride] were used as representatives of the group of AChE reactivators. Rat brain AChE was used as the appropriate source of the enzyme. Our results confirm that there is no single broad-spectrum oxime suitable for the treatment of poisoning with all highly toxic organophosphorus agents.
ESTHER : Kuca_2004_Neurotox.Res_6_565
PubMedSearch : Kuca_2004_Neurotox.Res_6_565
PubMedID: 15639788

Title : Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium--oximes - Kuca_2004_J.Enzyme.Inhib.Med.Chem_19_39
Author(s) : Kuca K , Patocka J
Ref : J Enzyme Inhib Med Chem , 19 :39 , 2004
Abstract : Cyclohexyl methylphosphonofluoridate (cyclosarin, cyclosin, GF) is a highly toxic organophosphate, which is resistant to conventional oxime therapy. To gain insight into the reactivation kinetics, rat brain acetylcholinesterase (AChE) was inhibited in vitro by cyclosarin (pH 8.0, 25 degrees C) and reactivated with 22 different pyridiniumoximes. Three compounds were shown to be superior to the other oximes: 4-carbamoyl-4'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)dipyridin-1-ium dichloride (HS-6), 4'-carbamoyl-2-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)dipyridin-1-ium dichloride (HI-6), and 4'-carbamoyl-2-[(hydroxyimino)-methyl]-1,1'-(but-2-ene-1,4-diyl)dipyridin-1-ium dichloride (BI-6).
ESTHER : Kuca_2004_J.Enzyme.Inhib.Med.Chem_19_39
PubMedSearch : Kuca_2004_J.Enzyme.Inhib.Med.Chem_19_39
PubMedID: 15202491

Title : Acetylcholinesterase and butyrylcholinesterase--important enzymes of human body - Patocka_2004_Acta.Medica.(Hradec.Kralove)_47_215
Author(s) : Patocka J , Kuca K , Jun D
Ref : Acta Medica (Hradec Kralove) , 47 :215 , 2004
Abstract : The serine hydrolases and proteases are a ubiquitous group of enzymes that is fundamental to many critical life-functions. Human tissues have two distinct cholinesterase activities: acetylcholinesterase and butyrylcholinesterase. Acetylcholinesterase functions in the transmission of nerve impulses, whereas the physiological function of butyrylcholinesterase remains unknown. Acetylcholinesterase is one of the crucial enzymes in the central and peripheral nerve system. Organophosphates and carbamates are potent inhibitors of serine hydrolases and well suited probes for investigating the chemical reaction mechanism of the inhibition. Understanding the enzyme's chemistry is essential in preventing and/or treating organophosphate and carbamate poisoning as well as designing new medicaments for cholinergic-related diseases like as Alzheimer's disease.
ESTHER : Patocka_2004_Acta.Medica.(Hradec.Kralove)_47_215
PubMedSearch : Patocka_2004_Acta.Medica.(Hradec.Kralove)_47_215
PubMedID: 15841900

Title : Determination of physostigmine and pyridostigmine in pharmaceutical formulations by capillary electrophoresis - Havel_2002_J.Capill.Electrophor.Microchip.Technol_7_107
Author(s) : Havel J , Patocka J , Bocaz G
Ref : J Capill Electrophor Microchip Technol , 7 :107 , 2002
Abstract : Physostigmine (PHY) and pyridostigmine (PYR) are two important anticholinesterase compounds with several clinical uses. Recently, PHY has been investigated for the treatment of senile dementia in Alzheimer's disease. However, both PHY and PYR have gained importance as antidotes for anticholinergic drugs. In military medicine, PYR is used as a prophylactic against nerve gas poisoning and was used in Saudi Arabia during the Gulf War in 1991. A new capillary zone electrophoresis (CZE) method for the rapid determination of PHY and PYR in pharmaceutical preparations has been developed. An untreated fused-silica capillary tube (75 microm i.d., 44 cm total length, 36.5 cm length to the detector) was employed with detection at 200 and 270 nm for PHY and PYR, respectively. The optimal separation conditions for PHY were: 50 mM boric acid-HCl buffer (pH 3.25) with 30 mM NaClO4, electrokinetic injection for 5 sec at -5 kV, temperature 25 degrees C, and separation voltage 15 kV. The optimal separation conditions for PYR were: 20 mM phosphate buffer (pH 7), electrokinetic injection for 20 sec at -10 kV, temperature 25 degrees C, and separation voltage 15 kV. The limits of detection (LOD, S/N = 3) were 70 and 60 ppb for PHY and PYR, respectively. The method can be used for the monitoring of possible main degradation products in tablets of military antidote formulations.
ESTHER : Havel_2002_J.Capill.Electrophor.Microchip.Technol_7_107
PubMedSearch : Havel_2002_J.Capill.Electrophor.Microchip.Technol_7_107
PubMedID: 12546159

Title : Effect of 7-methoxytacrine and L-carnitine on the activity of choline acetyltransferase - Bajgar_1999_Gen.Physiol.Biophys_18 Spec No_3
Author(s) : Bajgar J , Skopec F , Herink J , Patocka J , Kvetina J
Ref : Gen Physiol Biophys , 18 Spec No :3 , 1999
Abstract : Changes of choline acetyltransferase (ChAT) activity in the hippocampus and the basal ganglia were studied in rats treated i.p. with L-carnitine (CRT) and 7-methoxytacrine (7-MEOTA) (i.m.) separately or 3-days treated with L-carnitine and then with one administration of 7-MEOTA. Both compounds increased ChAT activity when administered separately. 3-day treatment of CRT followed by administration of 7-MEOTA normalized ChAT activity.
ESTHER : Bajgar_1999_Gen.Physiol.Biophys_18 Spec No_3
PubMedSearch : Bajgar_1999_Gen.Physiol.Biophys_18 Spec No_3
PubMedID: 10703712

Title : Capillary zone electrophoresis determination of galanthamine in biological fluids and pharmaceutical preparatives: experimental design and artificial neural network optimization - Pokorna_1999_Electrophoresis_20_1993
Author(s) : Pokorna L , Revilla A , Havel J , Patocka J
Ref : Electrophoresis , 20 :1993 , 1999
Abstract : Galanthamine is a third-generation cholinesterase inhibitor used against Alzheimer's disease. New analytical methods for the determination of galanthamine in pharmaceutical preparatives and biological fluids, such as urine and serum, were developed. An experimental design and artificial neural network approach were used for method optimization. Thirty-five ppb of galanthamine were determined in serum samples (with addition of 10 mM magnesium chloride and using solid-phase preconcentration).
ESTHER : Pokorna_1999_Electrophoresis_20_1993
PubMedSearch : Pokorna_1999_Electrophoresis_20_1993
PubMedID: 10451107

Title : Capillary zone electrophoretic determination of some drugs against Alzheimer's disease - Vargas_1998_J.Chromatogr.A_802_121
Author(s) : Vargas MG , Havel J , Patocka J
Ref : Journal of Chromatography A , 802 :121 , 1998
Abstract : A new capillary zone electrophoresis (CZE) method for the determination of tacrine (THA), 7-methoxytacrine (7-MTHA) and their basic metabolites (THAm, 7-MTHAm) in pharmaceutical and biological samples (urine and serum) was developed. Separation of all compounds by CZE was carried out using a 46.6 cm untreated fused-silica capillary applying 20 kV separation voltage using 50 mM phosphate buffer of pH 2.8 for THA and THAm and of pH 7.8 for 7-MTHA and 7-MTHAm as background electrolyte (BGE). Detection was carried out at 240 nm (THA and THAm) and 248 nm (7-MTHA and 7-MTHAm). THA and THAm were separated in less than 4 min while 7-MTHA and 7-MTHAm were separated in less than 7 min. The detection limits (SIN = 3) obtained were 3 ppb for THA and 4 ppb for 7-MTHA in aqueous solutions; 50 ppb for THA and 47 ppb for 7-MTHA for the determination in urine (diluted 1:10); 52 ppb for THA and 56 ppb for 7-MTHA, in deproteinized serum samples. The methods are suitable for therapeutic drug monitoring of the drugs.
ESTHER : Vargas_1998_J.Chromatogr.A_802_121
PubMedSearch : Vargas_1998_J.Chromatogr.A_802_121
PubMedID: 9588015

Title : Determination of the anti-Alzheimer's disease drugs tacrine, 7-methoxytacrine, and its metabolites by capillary zone electrophoresis -
Author(s) : Vargas MG , Havel J , Patocka J
Ref : Am Clin Lab , 17 :22 , 1998
PubMedID: 10181004

Title : Huperzine A--an interesting anticholinesterase compound from the Chinese herbal medicine - Patocka_1998_Acta.Medica_41_155
Author(s) : Patocka J
Ref : Acta Medica , 41 :155 , 1998
Abstract : Huperzine A, alkaloid from the Chinese herbal medicine Qian Ceng Ta, which is prepared from the moss Huperzia serrata, has been used in China for centuries to treat fever and inflammation. Huperzine A is a strong inhibitor of cholinesterases with high selectivity to acetylcholinesterase and in China is developed as therapeutic against Alzheimer's disease. May be that huperzine A will be better than other centrally active anticholinesterases in treating this neurodegenerative disorder. Huperzine A appears to have additional pharmacological properties that make it an attractive candidate therapy for clinical trials.
ESTHER : Patocka_1998_Acta.Medica_41_155
PubMedSearch : Patocka_1998_Acta.Medica_41_155
PubMedID: 9951045

Title : [Treatment of tardive dyskinesias with 7-methoxytacrine. I] - Hanus_1993_Sb.Ved.Pr.Lek.Fak.Karlovy.Univerzity.Hradci.Kralove.Suppl_36_37
Author(s) : Hanus H , Tuma I , Fusek J , Patocka J
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl , 36 :37 , 1993
Abstract : The 7-metoxytacrine (7-MEOTA) is an original Czech cholinergic agent synthetized in the labs of the Military Medical Academy in Hradec Kralove. The treatment of tardive dyskinesias is one of the possible indications of the use of 7-MEOTA in clinical practice. The authors have summed up their experience from the first phase of clinical tests with 7-MEOTA in psychiatrical patients suffering from tardive dyskinesias in long-termed administration of cholinergic agents. The clinical efficiency and tolerance of 7-MEOTA have been evaluated after a single administration of 100 mg of 7-MEOTA per os in 19 patients. A reduction of dyskinesias was observed as early as 4 h following the testing dose. In 5 patients, viz. in 26% a reduction of dyskinesias was observed of more than 50% of the original value of the total score of the testing scale AIMS. Except for a slight decrease of the blood pressure and a mild somnolence in 3 patients no other undesirable effects have been observed. In some patients a slight euphorization effect of 7-MEOTA has been found.
ESTHER : Hanus_1993_Sb.Ved.Pr.Lek.Fak.Karlovy.Univerzity.Hradci.Kralove.Suppl_36_37
PubMedSearch : Hanus_1993_Sb.Ved.Pr.Lek.Fak.Karlovy.Univerzity.Hradci.Kralove.Suppl_36_37
PubMedID: 8191251

Title : [Treatment of tardive dyskinesias with 7-methoxycrine. II] - Hanus_1993_Sb.Ved.Pr.Lek.Fak.Karlovy.Univerzity.Hradci.Kralove.Suppl_36_47
Author(s) : Hanus H , Tuma I , Fusek J , Patocka J
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl , 36 :47 , 1993
Abstract : In an open clinical study the authors have verified the effectivity and tolerance of 7-metoxytacrine cholinergic agent (7-MEOTA) in a total consisting of 14 patients with schizophrenic or schizoaffective psychoses suffering from tardive dyskinesias in long-termed treatment with neuroleptics. In the whole group consisting of 14 patients the seven days' administration of the experimental preparation in a dose of 100-150 mg pro die was evaluated. The 7-MEOTA preparation was administered to 7 patients for 2 weeks. In the seven and fourteen days' administration a favourable effect of 7-MEOTA on tardive dyskinesias was observed. A fast onset of the efficiency as early as in the first days of the treatment was recorded. In final evaluation a minimal reduction of 50% of the intensity of the dyskinesias (using the AIMS scale) in 29% of the patients treated for a fortnight was found. The 7-MEOTA preparation was well tolerated, no undesirable marked side effects being observed. A transient increase of ALT was found in 1 patient only in the 2nd week of the treatment. In experimental treatment the maintenance neuroleptical therapy was not discontinued. An improvement of the dyskinesias overlasted in some patients as long as 2 month g after the discontinuation of the administration of 7-MEOTA preparation.
ESTHER : Hanus_1993_Sb.Ved.Pr.Lek.Fak.Karlovy.Univerzity.Hradci.Kralove.Suppl_36_47
PubMedSearch : Hanus_1993_Sb.Ved.Pr.Lek.Fak.Karlovy.Univerzity.Hradci.Kralove.Suppl_36_47
PubMedID: 8191252

Title : [Biotransformation of the anticholinesterase agent, 9-amino-7-methoxy-1,2,3,4-tetrahydroacridine] - Patocka_1991_Cesk.Farm_40_130
Author(s) : Patocka J , Bielavsky J
Ref : Ceska Farmacie , 40 :130 , 1991
Abstract : Biotransformation of the anticholinesterasic agent 9-amino-7-methoxy-1,2,3,4-tetrahydroacridine was studied in the laboratory rat. In the animal urine, the main identified metabolites were 9-amino-7-hydroxy-1,2,3,4-tetrahydroacridine and its conjugate with glucuronic acid, or sulfuric acid, as well as 9-amino-1-hydroxy-7-methoxy-1,2,3,4-tetrahydroacridine and 9-amino-2-hydroxy-7-methoxy-1,2,3,4-tetrahydroacridine. A part of the drug was excreted in an unchanged form.
ESTHER : Patocka_1991_Cesk.Farm_40_130
PubMedSearch : Patocka_1991_Cesk.Farm_40_130
PubMedID: 2070431

Title : Tacrine in Alzheimer's disease -
Author(s) : Patocka J , Fusek J
Ref : Homeost Health Dis , 33 :161 , 1991
PubMedID: 1818685

Title : [9-amino-7-methoxy-1,2,3,4-tetrahydroacridine, a new substance with indirect cholinomimetic effects] -
Author(s) : Patocka J
Ref : Ceska Farmacie , 39 :29 , 1990
PubMedID: 2379246

Title : Inhibition of the butyrylcholinesterase by ethidium bromide - Patocka_1987_Biomed.Biochim.Acta_46_769
Author(s) : Patocka J
Ref : Biomedica Biochimica Acta , 46 :769 , 1987
Abstract : The effect of ethidium bromide (3,8-diamino-5-ethyl-6-phenyl-phenanthridinium bromide) on the activity of purified horse serum butyrylcholinesterase in vitro has been studied. Ethidium bromide is a middle reversible inhibitor with complex mixed competitive-noncompetitive inhibition kinetics. The inhibitor is bound to the anionic site of the enzyme surface.
ESTHER : Patocka_1987_Biomed.Biochim.Acta_46_769
PubMedSearch : Patocka_1987_Biomed.Biochim.Acta_46_769
PubMedID: 3446203

Title : The reactivation of O-isopropylmethylphosphonylated acetylcholinesterase and its modification by some non-acylating ligands -
Author(s) : Patocka J , Bajgar J
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove , 27 :477 , 1984
PubMedID: 6599821

Title : Some possibilities of protection against acetylcholinesterase inhibition by organophosphates in vivo -
Author(s) : Bajgar J , Patocka J , Fusek J , Hrdina V
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove , 27 :425 , 1984
PubMedID: 6599819

Title : Protective effect of 9-amino-7-methoxy-1,2,3,4-tetra-hydroacridine against inhibition of acetylcholinesterase by O-ethyl s-(2- dimethylaminoethyl) methylphosphonotioate in vivo -
Author(s) : Bajgar J , Fusek J , Patocka J , Hrdina V
Ref : Archives of Toxicology , 54 :163 , 1983
PubMedID: 6651529

Title : The influence of some drugs on the rat blood phosphodiesterase activity -
Author(s) : Bajgar J , Fusek J , Patocka J , Hrdina V
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove , 26 :423 , 1983
PubMedID: 6100335

Title : [Use of peritoneal dialysis in experimental organophosphate poisoning] -
Author(s) : Bajgar J , Fusek J , Patocka J , Hrdina V
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl , 25 :319 , 1982
PubMedID: 6985170

Title : In vivo kinetics of blood cholinesterase inhibition by 9-amino-1, 2, 3, 4-tetrahydroacridine, its 7-methoxy derivative and physostigmine in rats - Bajgar_1979_Physiol.Bohemoslov_28_31
Author(s) : Bajgar J , Fusek J , Patocka J , Hrdina V
Ref : Physiol Bohemoslov , 28 :31 , 1979
Abstract : In vivo inhibition of blood acetylcholinesterase activity by 9-amino-1, 2, 3, 4-tetrahydroacridine, its 7-methoxy derivative and physostigmine was studied in rats. Changes of enzyme activity in the blood were continually registered using an automatic colorimeter Auto Analyzer system. The dependence of % enzyme inhibition upon time in semilogarithmic transformation was characterized by a two phase curve. The first phase reflected the increase in the concentration of inhibitors in the blood during their resorption; this was followed by a slow second phase of inhibition. The inhibitory effect decreased in the order: physostigmine greater than tacrine greater than 7-methoxytacrine. The relationship between the anticholinesterase and antipsychotomimetic action of the examined substances is discussed.
ESTHER : Bajgar_1979_Physiol.Bohemoslov_28_31
PubMedSearch : Bajgar_1979_Physiol.Bohemoslov_28_31
PubMedID: 155828

Title : The interaction of anticholinesterases and diazepam in the treatment of anticholinergic syndrome in dogs -
Author(s) : Fusek J , Herink J , Koupilova M , Patocka J , Bajgar J , Hrdina V
Ref : Activitas Nervosa Superior (Praha) , 21 :183 , 1979
PubMedID: 517099

Title : Experimental therapy of poisoning with anticholinergic drugs in dogs -
Author(s) : Fusek J , Patocka J , Bajgar J , Herink J , Koupilova M , Hrdina V
Ref : Activitas Nervosa Superior (Praha) , 20 :80 , 1978
PubMedID: 636791

Title : Interaction of imipramine and 3-quinuclidyl benzilate with 9-amino-7-methoxy-1,2,3,4-tetrahydroacridine on the after-discharges in the limbic system -
Author(s) : Herink J , Fusek J , Bajgar J , Patocka J , Hrdina V
Ref : Activitas Nervosa Superior (Praha) , 20 :79 , 1978
PubMedID: 636789

Title : Actions of O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate and some pyridine aldoximes on isolated guinea-pigs heart atria - Fusek_1978_Acta.Biol.Med.Ger_37_347
Author(s) : Fusek J , Patocka J , Bajgar J
Ref : Acta Biologica et Medica Germanica , 37 :347 , 1978
Abstract : 1. The effects of acetylcholine and methylfurmetide on isolated guinea-pigs heart atria in the presence or absence of O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate (EDMM) were investigated. The influence of three cholinesterase reactivators on the heart atria pretreated with EDMM has been studied. 2. In the presence of EDMM, the negative inotropic effect of acetylcholine on the isolated heart atria was not significantly increased. This effect of methylfurmetide on heart atria was significantly decreased in the presence of EDMM. 3. EDMM alone caused negative inotropic and negative chronotropic effects depending on its concentration. These pharmacological effects were accompanied with inhibition of acetylcholinesterase activity in the heart muscle. 4. Addition of cholinesterase reactivators normalized the inotropic response of the isolated guinea-pig heart atria altered by EDMM and also increased the acetylcholinesterase activity in the heart.
ESTHER : Fusek_1978_Acta.Biol.Med.Ger_37_347
PubMedSearch : Fusek_1978_Acta.Biol.Med.Ger_37_347
PubMedID: 706945

Title : Continual determination of acetylcholinesterase inhibition following organophosphate poisoning using an auto analyzer - Bajgar_1977_Acta.Biol.Med.Ger_36_231
Author(s) : Bajgar J , Fusek J , Patocka J , Hrdina V
Ref : Acta Biologica et Medica Germanica , 36 :231 , 1977
Abstract : A modification for continual monitoring of the blood acetylcholinesterase activity in the rat on an auto analyzer system was described. With using this technique, inhibition of the enzyme in vitro with O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate was determined. Bimolecular rate constant and I50 values were 1.66-10(6) M-1-min-1 and 1.4-10(-8)M, respectively. Rats treated i.m. with 0.043 mg/kg of this compound showed fast and rapid inhibition of the blood acetylcholinesterase after intoxication. The bimolecular rate constant of inhibition in vivo, calculated analogously as that in vitro was 1.37-10(6) M-1-min-1. On the presumption that both rates of inhibition (in vitro and in vivo) are identical, the concentration of organophosphate producing inhibition effect in vivo was 82% of the dose administered.
ESTHER : Bajgar_1977_Acta.Biol.Med.Ger_36_231
PubMedSearch : Bajgar_1977_Acta.Biol.Med.Ger_36_231
PubMedID: 906734

Title : The effects of some cholinesterase reactivators on contractility of the isolated guinea-pig heart atria - Fusek_1976_Acta.Biol.Med.Ger_35_657
Author(s) : Fusek J , Patocka J
Ref : Acta Biologica et Medica Germanica , 35 :657 , 1976
Abstract :
ESTHER : Fusek_1976_Acta.Biol.Med.Ger_35_657
PubMedSearch : Fusek_1976_Acta.Biol.Med.Ger_35_657
PubMedID: 983615

Title : Anticholinesterase action of 3-diethylaminophenyl-N-methyl-carbamate methiodide in vitro and in vivo - Bajgar_1976_Acta.Biol.Med.Ger_35_479
Author(s) : Bajgar J , Patocka J
Ref : Acta Biologica et Medica Germanica , 35 :479 , 1976
Abstract : The inhibitory effect of 3-diethylaminophenyl-N-methylcarbamate methiodide on rat brain acetylcholinesterase and horse plasma butyrylcholinesterase was studied in vitro. This quaternary carbamate is a more potent inhibitor of acetylcholinesterase than butyrylcholinesterase. Complete inhibition of acetylcholinesterase may be achieved without any inhibition of butyrylcholinesterase, i.e. that 3-diethylaminophenyl-N-methylcarbamate methiodide is a selective inhibitor of acetylcholinesterase. The inhibitory effect of different doses of this compound on plasma and liver butyrylcholinesterase and erythrocyte, brain, heart and diaphragm acetylcholinesterase of the rat was studied in vivo. With increasing doses of carbamate the inhibition of the enzymes in the plasma, erythrocytes, liver, heart, and diaphragm increased while the brain acetylcholinesterase was unaffected. The toxic action of carbamate studied was preferably due to acetylcholin esterase inhibition in the peripheral nervous system and this compound cannot penetrate the blood-brain barrier.
ESTHER : Bajgar_1976_Acta.Biol.Med.Ger_35_479
PubMedSearch : Bajgar_1976_Acta.Biol.Med.Ger_35_479
PubMedID: 970052

Title : The influence of O-isopropyl-S-(2-dimethylaminoethyl) methylphosphonothioate on tissue cholinesterases of the guinea pig -
Author(s) : Bajgar J , Patocka J , Jakl A
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl , 16 :225 , 1973
PubMedID: 4528764

Title : Reactivation of isopropyl-methylphosphonylated acetylcholinesterase by , -bis-(4-hydroxyimino-methylpyridinium)-2-trans-butene dibromide--the effect of pH -
Author(s) : Patocka J , Bielavsky J
Ref : Biochemical Pharmacology , 21 :742 , 1972
PubMedID: 5063172

Title : Affinity of human brain acetylcholinesterase to some organophosphates and carbamates in vitro -
Author(s) : Patocka J , Bajgar J
Ref : Journal of Neurochemistry , 18 :2545 , 1971

Title : The inhibition of human brain acetylcholinesterase by LSD-25 and JB-336 in vitro -
Author(s) : Bajgar J , Patocka J , Zizkovsky V
Ref : Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl , 14 :417 , 1971
PubMedID: 5291385

Title : Reactivating effect of alpha,omega-bis-(4-pyridinealdoxime)-2-trans-butene dibromide on isopropyl-methylphosphonylated acetylcholinesterase -
Author(s) : Patocka J , Bielavsky J , Ornst F
Ref : FEBS Letters , 10 :182 , 1970
PubMedID: 11945389

Title : Some enzymatic properties of human brain acetylcholinesterase -
Author(s) : Patocka J , Bajgar J
Ref : FEBS Letters , 2 :195 , 1969
PubMedID: 11946310