• MeSH
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• hematoencefalická bariéra MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   MeSH
• pyridostigmin-bromid aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• chemie farmaceutická metody   MeSH
• cholinesterasové inhibitory analýza   izolace a purifikace   MeSH
• elektroforéza kapilární metody   MeSH
• finanční podpora výzkumu jako téma MeSH
• fysostigmin analýza   MeSH
• indikátory a reagencie MeSH
• pyridostigmin-bromid analýza   MeSH

The protective effect of the reversible cholinesterase inhibitors tacrine and pyridostigmine alone or in combination with different drugs against acetylcholinesterase inhibition in the pontomedullar area and cerebellum of rats caused by VX agent (O-ethyl S-2-diisopropylaminoethyl methyl phosphonothiolate) in vivo (2xLD50) was studied along with survival of animals pretreated with different combinations of the drugs used. The best prophylactic effect was observed in a combination of pyridostigmine with benactyzine, trihexyphenidyle and HI-6. Tacrine alone or in other combinations has had no better prophylactic effect in comparison with these combinations containing pyridostigmine. Equine butyrylcholinesterase, also protected against VX poisoning very effectively.

• MeSH
• chemické bojové látky toxicita   MeSH
• cholinesterasové inhibitory terapeutické užití   toxicita   MeSH
• financování organizované MeSH
• krysa rodu rattus MeSH
• mozek účinky léků   MeSH
• neurotoxické syndromy prevence a kontrola   MeSH
• organothiofosforové sloučeniny toxicita   MeSH
• potkani Wistar MeSH
• pyridostigmin-bromid farmakologie   MeSH
• takrin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH

The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC-37, PC-48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman-induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising.

• MeSH
• antidota terapeutické užití   MeSH
• cholinesterasové inhibitory terapeutické užití   MeSH
• LD50 MeSH
• myši MeSH
• piperaziny terapeutické užití   MeSH
• pyridostigmin-bromid terapeutické užití   MeSH
• soman antagonisté a inhibitory   otrava   MeSH
• takrin analogy a deriváty   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• MeSH
• atropin aplikace a dávkování   terapeutické užití   MeSH
• cholinesterasové inhibitory terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• krysa rodu rattus MeSH
• LD50 MeSH
• myši MeSH
• organofosfáty toxicita   MeSH
• parasympatolytika terapeutické užití   MeSH
• pyridostigmin-bromid aplikace a dávkování   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

AIM: The ability of four newly prepared reversible inhibitors of acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and currently used carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated. METHODS: The evaluation of the effect of pharmacological pretreatment is based on the identification of changes of soman-induced toxicity that was evaluated by the assessment of its LD50 value and its 95% confidence limit using probitlogarithmical analysis of death occurring within 24 h after administration of soman. RESULTS: 6-chlorotacrine was only able to markedly protect mice against acute toxicity of soman. In addition, the pharmacological pretreatment with 6-chlorotacrine or compound 2 was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. The other newly prepared reversible inhibitors of acetylcholinesterase (7-phenoxytacrine, compound 1) as well as commonly used pyridostigmine did not influence the efficacy of antidotal treatment. CONCLUSION: These findings demonstrate that pharmacological pretreatment of somanpoisoned mice can be promising and useful in the case of administration of 6-chlorotacrine and partly compound 2.

• MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• isochinoliny MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• myši MeSH
• pyridinové sloučeniny aplikace a dávkování   farmakologie   MeSH
• pyridostigmin-bromid farmakologie   MeSH
• soman otrava   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50) value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre-treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising.

• MeSH
• antidota aplikace a dávkování   farmakologie   MeSH
• atropin aplikace a dávkování   farmakologie   MeSH
• chemické bojové látky otrava   MeSH
• cholinesterasové inhibitory aplikace a dávkování   farmakologie   MeSH
• isochinoliny aplikace a dávkování   farmakologie   MeSH
• kombinovaná farmakoterapie MeSH
• LD50 MeSH
• myši MeSH
• oximy aplikace a dávkování   farmakologie   MeSH
• pyridinové sloučeniny aplikace a dávkování   farmakologie   MeSH
• pyridostigmin-bromid aplikace a dávkování   farmakologie   MeSH
• reaktivátory cholinesterázy aplikace a dávkování   farmakologie   MeSH
• soman aplikace a dávkování   otrava   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• MeSH
• cholinergní látky aplikace a dávkování   škodlivé účinky   MeSH
• fyziologický stres prevence a kontrola   účinky léků   MeSH
• kombinovaná farmakoterapie metody   MeSH
• krysa rodu rattus MeSH
• soman aplikace a dávkování   škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• acetylcholinesterasa chemie   MeSH
• benaktyzin aplikace a dávkování   farmakologie   MeSH
• chemické bojové látky farmakologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• myši MeSH
• oximy aplikace a dávkování   farmakologie   MeSH
• pyridostigmin-bromid analogy a deriváty   aplikace a dávkování   farmakologie   MeSH
• sarin analogy a deriváty   aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors - pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.

• MeSH
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory farmakologie   terapeutické užití   MeSH
• deriváty atropinu * MeSH
• donepezil farmakologie   MeSH
• hypertenze * farmakoterapie   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• pyridostigmin-bromid * farmakologie   MeSH
• srdeční frekvence MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH