A comparison of cholinesterase inhibitors in the treatment of quinuclidinyl benzilate-induced behavioural deficit in rats performing the multiple T-maze

Mišík, Ján; Kassa, Jiřı́

doi:10.1016/j.jab.2014.01.006

Cited by 12 publications

(9 citation statements)

References 45 publications

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“…These drugs are taken with respect to the overall patient's condition in the individual stage of AD . However, the effects of these drugs vary at each individual (Misik and Kassa, 2014). Moreover, these drugs do not improve patient's social conditions.…”

Section: Current Treatment Of Admentioning

confidence: 99%

Alzheimer's disease: Potential preventive, non-invasive, intervention strategies in lowering the risk of cognitive decline - A review study

Klímová¹,

Kuča²

2015

J Appl Biomed

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Section: Current Treatment Of Admentioning

confidence: 99%

Alzheimer's disease: Potential preventive, non-invasive, intervention strategies in lowering the risk of cognitive decline - A review study

Klímová¹,

Kuča²

2015

J Appl Biomed

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“…As a standard amnesic drug, scopolamine is frequently used in similar 50 was not established, the therapeutic dose was approximated from a previous study 36 . studies [32][33][34][35] .…”

Section: Discussionmentioning

confidence: 99%

“…In this study, scopolamine was successfully substituted by another non-selective muscarinic receptor antagonist -QNB. This approach enabled long-term observation of anti-cholinergic effects due to the prolonged action of QNB compared to scopolamine 27,36 . To evaluate the pro-cognitive effects of novel compounds, the multiple T-maze test was selected 26,34,37,38 .…”

Section: Discussionmentioning

confidence: 99%

“…Selected standards donepezil and tacrine have been confirmed as cognitive enhancers in several different animal models of neurodegenerative disorders 7,8,41,42 . Donepezil was usually more effective than tacrine, but the difference could be attributed to variable therapeutic doses 36 . In this study, the effects of both standards were equivalent at all time points.…”

Section: Discussionmentioning

confidence: 99%

“…An advantage in favour of donepezil against tacrine is better central activity and selectivity to acetylcholinesterase [43][44][45] and also reduced incidence of peripheral side effects due to lower toxic potential at therapeutic doses. The narrow therapeutic index of tacrine explains for the failure of tacrine (10 mg/kg) in the multiple T-maze test due to cholinergic overstimulation 36 . Novel ChEIs were at least equally effective to standards in the 1 h test.…”

Section: Discussionmentioning

confidence: 99%

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The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test

Mišík¹,

Korábečný²,

Nepovimová³

et al. 2015

BIOMED PAP

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Aims. The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods. Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results. QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease.

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Simple validated method of LC–MS/MS determination of BZ agent in rat plasma samples

Herman

Dlabková

Cechova

et al. 2020

Drug Testing and Analysis

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Agent BZ (3‐quinuclidinyl benzilate) is a centrally acting synthetic anticholinergic agent, considered as a potential military incapacitating chemical warfare agent. Despite its significance as a model compound in pharmacological research and its potential misuse in chemical attacks, few modern analytical methods for BZ determination in biological samples have been published. The goal of the present work is to develop and validate a sensitive and rapid LC–MS/MS method for the determination of agent BZ in rat plasma. The sample preparation was based on solid‐phase extraction on C‐18 cartridges. The reversed‐phase HPLC coupled with the mass spectrometer with electrospray ionization in the positive ion‐selective reaction monitoring mode was employed in the BZ analysis. Atropine was used as an internal standard. The presented method is selective, accurate, precise, and linear (r2 = 0.9947) in a concentration range from 0.5 ng/mL to 1 000 ng/mL and sensitive enough (limit of detection 0.2 ng/mL; limit of quantification 0.5 ng/mL) to determine the BZ plasma levels in rats exposed to 2 mg/kg and 10 mg/kg of BZ. The highest level of BZ in plasma was observed 5 minutes after intramuscular administration (154.6 ± 22.3 ng/mL in rats exposed to 2 mg/kg of BZ and 1024 ± 269 ng/mL in rats exposed to 10 mg/kg). After 48 h, no BZ was observed at detectable levels. This new method allows the detection and quantification of BZ in biological samples after exposure of an observed organism and it will be further optimized for other tissues to observe the distribution of BZ in organs.

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A comparison of cholinesterase inhibitors in the treatment of quinuclidinyl benzilate-induced behavioural deficit in rats performing the multiple T-maze

Cited by 12 publications

References 45 publications

Alzheimer's disease: Potential preventive, non-invasive, intervention strategies in lowering the risk of cognitive decline - A review study

Alzheimer's disease: Potential preventive, non-invasive, intervention strategies in lowering the risk of cognitive decline - A review study

The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test

Simple validated method of LC–MS/MS determination of BZ agent in rat plasma samples

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