Anticholinergic Activity Research Articles

Anti-cholinergic activities of Turkish Corydalis DC. species

The aim of the present study is to determine the in vitro cholinesterase inhibitory effects of the tubers of Corydalis DC. species growing in Turkey belonging to Papaveraceae family. This genus comprises of approximately 470 species distributed in the world and is represented 17 species and 22 taxons, 8 of which are endemic, in the flora of Turkey. Some Corydalis species are used in folk medicine for the memory enhancement in Europe and China. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the ethanolic extracts prepared from tubers collected from 54 populations are screened by the slightly modified spectrophotometric method. The highest anticholinesterase compound/s were determined by assay-guided fractionation and their structures were elucidated through chromatographic (LC-Q-ToF-MS) and extensive spectroscopic techniques. According to the results, canadine, berberine and dehydrocorydaline from protoberberine-type isoquinoline alkaloids were exerted the most potent inhibitory effect against two enzymes. This is the first study determining anticholinesterase compounds of Corydalis species growing in Turkey.

Inhibitory Effects of Antipsychotics on the Contractile Response to Acetylcholine in Rat Urinary Bladder Smooth Muscles.

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.

Centrally-acting anticholinergic drugs– associations with mortality, hospitalisation and cognitive decline following dementia diagnosis in people receiving antidepressant and antipsychotic drugs

Objectives Long-term use of anticholinergic medication in older people is associated with increased risk of cognitive decline and mortality, but this relationship could be confounded by the underlying illness the drugs are treating. To investigate associations between central anticholinergic antidepressants or antipsychotics and mortality, hospitalisation and cognitive decline in people with dementia. Method In cohorts of patients with a dementia diagnosis receiving antidepressant and/or antipsychotic medication (N = 4,380 and N = 2,335 respectively), assembled from a large healthcare database, central anticholinergic burden scores were estimated using the Anticholinergic Effect on Cognition (AEC) scale. Data were linked to national mortality and hospitalisation data sources, and Mini-Mental State Examination (MMSE) scores were used to investigate cognitive decline. Results There was a reduced mortality risk in people receiving agents with high central anticholinergic burden compared to those with no or low burden which was statistically significant in the antidepressant cohort (Hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.79-0.98; p = 0.023) but not the antipsychotic one (HR: 0.91; 95% CI: 0.82-1.02; p = 0.105). Patients on antidepressants with no central anticholinergic burden had accelerated cognitive decline compared with other groups, whereas no differences were found in the antipsychotic cohort. No significant associations were detected between antidepressant or antipsychotic-related central anticholinergic burden and hospitalisation. Conclusion These counter-intuitive findings may reflect factors underlying the choice of psychotropics rather than the agents themselves, although do not support a strong role for central anticholinergic drug actions on dementia outcomes. Further studies, including randomized switching of agents are needed to clarify this relationship.

The impact of long-term exposure to anticholinergics among people with intellectual disabilities: a scoping review protocol

Background: Older adults with intellectual disability often take multiple medicines with anticholinergic activity and sedative properties to manage multi-morbidity; the use of medication with anticholinergic activity has been found to be associated with various cognitive and physical impairments. However, there are limited studies that have examined the long-term impact of anticholinergic use among older adults. Therefore, this protocol is designed to conduct a scoping review to examine the available data on the long-term impact of anticholinergic use in older adults with intellectual disability. Aim and objectives: The aim of this scoping review is to a) map and b) examine the existing research literature to answer the research question: What is the impact on cognitive and physical outcomes of long-term exposure to medications with anticholinergic activity among older adults with intellectual disabilities? Methods and analysis: This scoping review will follow the methodology framework of Arksey and O’Malley and its developed version by Levac. The framework consists of a six-stage process to be conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) reporting guidelines. The search strategy will include the following electronic data bases: Pubmed, Cochrane library, EMBASE, Medline, Science Direct, CINAHL Complete and PsycINFO. The search will include terms related to ‘Anticholinergic burden’, ‘Intellectual disability’, ‘Adverse drug reaction’ and ‘long-term impact’ with Boolean operator ‘and’. The scoping review will include studies with at least 3 months exposure to anticholinergics. The collected data will be mapped as a tabular presentation of the various physical and cognitive adverse effects associated with long-term use of anticholinergics in this group of population.

Nickel(II)–meclofenamate complexes: Structure, in vitro and in silico DNA– and albumin–binding studies, antioxidant and anticholinergic activity

Five novel nickel(II) complexes with the non–steroidal anti–inflammatory drug sodium meclofenamate (Na–mclf) have been synthesized and characterized in the absence or co–existence of the nitrogen–donors imidazole (Himi), 2,2′–bipyridylamine (bipyam), 2,2′–bipyridylketoxime (Hpko) and 2,9–dimethyl–1,10–phenanthroline (neoc); namely [Ni(mclf–O)2(Himi)2(MeOH)2], [Ni(mclf–O)2(MeOH)4], [Ni(mclf–O)(mclf–O,O′)(bipyam)(MeOH)]·0.25MeOH, [Ni(mclf–O,O′)2(neoc)] and [Ni(mclf–O)2(Hpko–N,N′)2]·MeOH·0.5H2O. The affinity of the complexes for calf–thymus (CT) DNA was investigated by various techniques and intercalation is suggested as the most possible interaction mode. The interaction of the complexes for bovine and human serum albumins was also investigated in order to determine the binding constants, concluding that the complexes bind reversibly to albumins for the transportation towards their target cells or tissues and their release upon arrival at biotargets. The antioxidant activity of the compounds was evaluated via their ability to scavenge 1,1–diphenyl–picrylhydrazyl and 2,2′–azinobis(3–ethylbenzothiazoline–6–sulfonic acid) free radicals and to reduce H2O2. For the determination of the anticholinergic ability of the complexes the in vitro inhibitory activity against the enzymes acetylcholinesterase and butyrylcholinesterase was evaluated and presented promising results. The in silico molecular modeling calculations employed provide useful insights for the understanding of the mechanism of action of the studied complexes at a molecular level. This applies on both the impairment of DNA by its binding with the studied complexes and transportation through serum albumins, as well as the ability of these compounds to act as anticholinergic agents.

Anticholinergic, Antidiabetic and Antioxidant Activities of Ferula orientalis L. Determination of Its Polyphenol Contents by LC-HRMS

To evaluate the antioxidant activity of evaporated ethanolic extract of Ferula orientalis L. (EEFO) and lyophilized water extract of Ferula orientalis L. (WEFO) several in vitro antioxidant methods such as ABTS•+ scavenging activity, DPPH· scavenging activity, Fe3+reduction method, cupric ions (Cu2+) reduction capacity, and metal ion (Fe2+)-binding activities using ferrozine reagent were separately performed. Also, BHT, α-tocopherol and ascorbic acid were used as the standard antioxidant molecules. Moreover, some phenolic compounds that are responsible for antioxidant abilities of EEFO and WEFO were determined by LC-HRMS. EEFO and WEFO demonstrated effective antioxidant abilities when compared with the standards. EEFO demonstrated IC50 values of 1.946 µg/mL against acetylcholinesterase (AChE), 0.815 µg/mL against α-glycosidase, and 0.675 µg/mL against α-amylase.

Phytochemical profiles and antioxidant, anticholinergic, and antidiabetic activities of Odontites serotina (Lam.) Dum

IntroductionOdontites serotina is a medicinal plant primarily distributed in northern China. To the best of our knowledge, no previous study has investigated the bioactivities of this plant. The present study investigated the active constituent contents and bioactivities of the 95% ethanol crude extract (ECE) of O. serotina and its fractions. MethodsThe total phenol/flavonoid/iridoid glycoside contents were examined by spectrophotometric methods. DPPH/ABTS assays were used to evaluate the antioxidant activities. α-Glycosidase/α-amylase/AChE/BChE-inhibitory assays were performed to evaluate antidiabetic and anticholinergic activities. Correlations were determined via Pearson's correlation analyses. ResultsThe total phenol/flavonoid contents of the ethyl acetate fraction (EAF) and n-butanol fraction (NBF) and the total iridoid glycoside content of the NBF were determined to be significantly higher than those of the ECE. The EAF and NBF exhibited strong antioxidant and potent inhibitory effects on acetylcholinesterase (AChE), and they also exhibited butylcholinesterase (BChE)/α-glucosidase-inhibitory effects. No sample demonstrated any effects against α-amylase. The correlation analyses indicated strong positive correlations between total phenol content and antioxidant activity and between total flavonoid content and antioxidant/AChE/BChE/α-glucosidase-inhibitory activities. The isolation of the EAF resulted in the acquisition of acteoside (1), emodin (2), benzoic acid (3) and β-sitosterol (4). Acteoside showed moderate antioxidant and BChE/α-glucosidase-inhibitory activities, and emodin exhibited moderate BChE-inhibitory activity. ConclusionThe EAF and NBF are rich in phenols, flavonoids and iridoid glycosides and have antioxidant and dual AChE/BChE and selective α-glycosidase-inhibitory activities. O. serotina has potential in the development of new drugs to treat Alzheimer's disease (AD) and diabetes.

Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) – profiling of phenolic compounds by LC-HRMS

In order to evaluate the antioxidant activity of evaporated ethanolic extract (EESB) and lyophilized water extract (WESB) of Shaggy bindweed (Convulvulus betonicifolia Mill. Subs), some putative antioxidant methods such as DPPH· scavenging activity, ABTS•+ scavenging effect, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+) binding activities were separately performed. Also, ascorbic acid, α-tocopherol and BHT were used as the standard compounds. Additionally, some phenolic compounds that responsible for antioxidant abilities of EESB and WESB were screened by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the same concentration, EESB and WESB demonstrated effective antioxidant abilities when compared to standards. In addition, EESB demonstrated IC50 values of 1.946 μg/mL against acetylcholinesterase (AChE), 0.815 μg/mL against α-glycosidase and 0.675 μg/mL against α-amylase enzymes.

Determination of clemastine by the HPLC method in the blood

Topicality. Сlemastine fumarate (tavegil)-1-methyl-2 [2-α-methyl-p-chlorobenzhydryloxy)-ethyl]-pyrrolidine fumarate is the first generation H1-histamine receptor blocker. Сlemastine fumarate selectively inhibits histamine H1 receptors and reduces capillary permeability. The drug has a pronounced anti-allergic and antipruritic effect. Clemastine prevents the development of vasodilation and the smooth muscle contraction induced by histamine. Сlemastine fumarate has an isignificant anticholinergic activity, causes sedation. The drug is used to treat pruritus in psoriasis, multiple sclerosis and optic neuritis. Clemastine is characterized by the following side effects: increased fatigue, drowsiness, sedation, weakness, lethargy, impaired coordination of movements; nausea, vomiting, decreased blood pressure, palpitations, hemolytic anemia, skin rash, anaphylactic shock. In case of an overdose, the drug has a neurotoxic effect, which manifests itself in impaired consciousness with the development of generalized anticholinergic convulsive syndrome. The urgent task for monitoring the treatment effectiveness of the population with сlemastine fumarate and diagnosis of drug intoxication is the choice of highly sensitive and selective research methods of its analysis in pharmaceuticals and biological matrices during the treatment. Aim. To develop an algorithm for directed analysis of clemastine in biological extracts from the blood using a unified method of the HPLC research. Materials and methods. The extraction of clemastine was performed with chloroform at Ph 9.0. The extracts were purified from impurities by a combination of TLC and extraction with hexane. The TLC purification and identification of clemastine were carried out under optimal conditions: the system of organic solvents – methanol – 25 % solution of ammonium hydroxide (100 : 1.5) and chromatographic plates – Sorbfil PTLC-AF-A, Rf сlemastine = 0.60 ± 0.03. To detect clemastine, the most sensitive location reagents were used –UV light (λ = 254 nm) and Dragendorff’s reagent modified by Mounier. The chromatographic analysis was performed on a “Milichrome A-02” microcolumn liquid chromatograph (EkoNova, Closed Joint-Stock Company, Russia) under standardized HPLC conditions: the reversed-phase variant using a metal column with a non-polar absorbent Prontosil 120-5C 18 AQ, 5 μm; the mobile phase in the linear gradient mode – from eluent А (5 % acetonitrile and 95 % buffer solution – 0.2 М solution of lithium perchlorate in 0.005 М solution of perchloric acid) to eluent B (100 % acetonitrile) for 40 min. Regeneration of the column was conducted for 2 min with the mixture of solvents; the flow rate of the mobile phase was 100 μl/min, the injection volume – 4 μl. The multichannel detection of the substance was performed using a two-beam multi-wave UV spectrophotometer at 8 wavelengths of 210, 220, 230, 240, 250, 260, 280, and 300 nm; the optimal value of the column temperature – 37-40 °С and the pump pressure – 2.8-3.2 MPa. Results and discussion. Isolation of clemastine from the blood was performed according to the method developed, including the extraction with chloroform at pH 9.0; the extraction purification of extracts with hexane from impurities; the TLC purification and identification of clemastine. Using the unified HPLC method clemastine was identified by retention parameters and spectral ratios. For the quantitative determination, a calibration graph or the straight line equation corresponding to this graph were used. The results obtained indicated the reliability and reproducibility of the method. It was found that the relative uncertainty of the average result in the analysis of clemastine in the blood was ε = ± 4.63 %, the relative standard deviation of the average result was RSDx = 1.67 %. Conclusions. Clemastine was extracted with chloroform at pH 9.0 from the blood. Purification of extracts from co-extractive compounds was performed by combining TLC and extraction with hexane. It has been found that when isolating сlemastine from the blood according to the methods developed it is possible to determine 36.05-39.55 % of the substance (ε = ± 4.63 %, RSDx = 1.67 %). The method of TLC purification and identification of сlemastine in biogenic extracts was tested under the optimal conditions: the system of organic solvents – methanol – 25 % solution of ammonium hydroxide (100 : 1.5), the use of reagents – UV light, Dragendorff’s reagent modified by Mounier, Rf сlemastine = 0.60 ± 0.03 (Sorbfil PTLC-AF-A). The unified HPLC method for identification and quantification of сlemastine was tested in biogenic extracts from the blood according to the algorithm of the directed analysis developed. It has been found that сlemastine can be identified by the retention time – 25.997-26.011 min; the retention volume – 2599.7-2601.1 μl; spectral ratios – 0.741; 0.536; 0.096; 0.023; 0.027; 0.005; 0.003. The сlemastine content was determined by the equation S = 0.15 · 10-3 С + 0.14 · 10-3; the correlation coefficient was equal to 0.9998. Chromatographic methods can be recommended for implementation in practice of the Bureau of Forensic Medical Examination, poison control centers, clinical laboratories regarding the study of medicinal substances in biological objects.

Impact of Multiple Prescriptions With Anticholinergic Properties on Adverse Clinical Outcomes in the Elderly: A Longitudinal Cohort Study in Taiwan.

The cumulative effect of multiple pharmaceutics with anticholinergic properties (i.e., anticholinergic burden), can serve as an indicator of suboptimal prescribing in the elderly. Yet, no research is available concerning the effect of different compositions of score on adverse outcomes under the same anticholinergic burden. This population-based cohort study investigated whether different combinations of medications with anticholinergic properties have different impacts on adverse outcomes in the elderly using the Anticholinergic Risk Scale (ARS) and Anticholinergic Cognitive Burden Scale (ACB) scores. We included 116,043 people aged 65years and older from Taiwan's Longitudinal Health Insurance Database and measured their monthly anticholinergic burden over a 10-year follow-up period (from January 1, 2002, to December 31, 2011). We analyzed the association between different anticholinergic score compositions and adverse outcomes (emergency department visits, all-cause hospitalizations, fracture-specific hospitalizations, and incident dementia) via generalized estimating equations. Cumulative effects of multiple medications with low anticholinergic activity were associated with a greater risk for emergency department visits and all-cause hospitalizations (emergency department visits for 65-74year olds (y/o): ACB 1+1+1, adjusted odds ratio (aOR) 2.05 (1.99-2.12); ACB 1+2, aOR 2.04 (1.91-2.17); and ACB 3, aOR 1.62 (1.57-1.66)). In contrast, using medications with greater potency had a greater impact on central adverse outcomes (incident dementia for 65-74 y/o: ACB 1+1+1, aOR 3.30 (2.84-3.84); ACB 1+2, aOR 5.84 (4.59-7.41); and ACB 3, aOR 9.15 (8.38-9.99)). The quantity of anticholinergics (even with low score) an older person used matters in risk of emergency department visit and all-cause hospitalization but the potency of anticholinergics (i.e., those with high score) matters in risk of fracture-specific hospitalization and incident dementia.

Angioedema with haloperidol - case report

IntroductionHaloperidol is a high-potency first generation antipsychotic and one of the most frequently used antipsychotic medications. It is a potent central antagonist of type 2 dopamine receptors, with low alpha 1 adrenergic activity and has no antihistamine or anti-cholinergic activity. It is a widely used drug with proven efficacy. Angioedema is a very rare side effect, occurring in <1% of cases.ObjectivesCase report and reflection on its etiologyMethodsA Pubmed search was performed with the MeSH terms “haloperidol” and “Anaphylactic reactions”. Relevant articles obtained from the respective bibliographic references were also consulted.ResultsThe following case describes the development of angioedema in a patient with an acute confusional syndrome on the second haloperidol IM administration for symptomatic control of agitation. Angioedema has been reported as an adverse effect of various antipsychotics such as clozapine, risperidone, ziprazidone and chlorpromazine, however, resulting from haloperidol administration is rare.ConclusionsIn long-term formulations sensitization testing is especially important but a single prior administration is not sufficient, a second controlled administration is essential to avoid this kind of fatal reactions.

CUMULATIVE CHOLINOLYTIC EFFECT IN CLINICAL PRACTICE (LITERATURE REVIEW)

Anticholinergic agents are widely used in clinical practice. However, they can cause various cumulative side effects (dry mouth, drowsiness, confusion, residual urine accumulation, etc.). The purpose of the study is to perform an analytical review of the literature dedicated to causes, complications and rehabilitation of patients with cumulative anticholinergic effect. The analytical review of the literature highlights the risks and benefits of using anticholinergic drugs. Anticholinergic agents make up to one third of all medicines for the aged people. Recent data have proved the relationship between the long-term use of anticholinergics and dementia. New results relating to the cholinergic system in the regulation of cerebral vascularisation and in neuritis indicate that anticholinergics may contribute to the absolute risk and progression of neurodegenerative diseases. It has been proven that more than 600 drugs taken by aged patients carry the so-called "anticholinergic load". The number of drugs with anticholinergic properties is constantly increasing, they include: antidepressants, antihistamines, antiparkinsonian, antipsychotic, antispasmodic, mydriatic drugs, drugs for the treatment of overactive bladder and many others. Conclusions. The number of drugs that have anticholinergic activity and can cause complications associated with anticholinergic load is increasing. To assess the anticholinergic action of drugs, several methods have been proposed, taking into account the amount of dose and the intensity of anticholinergic activity of drugs. The research of the general medical community about the anticholinergic load problem and high alertness when prescribing drugs with anticholinergic properties can prevent the cumulative anticholinergic effect development and severe complications, and, thus, save the life and health of patients.

Relationships Between a New Cultured Cell-Based Serum Anticholinergic Activity Assay and Anticholinergic Burden Scales or Cognitive Performance in Older Adults

Anticholinergic burden has been associated with deleterious effects on cognition particularly in those with an underlying brain disorder. We developed a new assay based on cultured cells to measure serum anticholinergic activity (cSAA). We report on its relationships with established anticholinergic burden rating scales and cognitive assessments in older patients with mild cognitive impairment (MCI) or major depressive disorder (MDD) in remission or both. The study was cross sectional in nature. This was a five-centre study conducted in Toronto, Canada. Serum samples were collected and cSAA levels were measured in 311 participants aged 60 years or older (154 with MCI, 57 with MDD, and 100 with MCI + MDD). The cSAA assay uses radio-ligand binding to cultured cells stably expressing the muscarinic M1 receptors, with an added procedure to remove potential confounds associated with serum proteins. Lists of medications were used to calculate Anticholinergic Burden and Anticholinergic Drug Scale total scores. Participants also completed a comprehensive cognitive battery. Higher cSAA levels were associated with higher anticholinergic burden and anticholinergic drug scale scores, and also with lower performance on executive function tests, after adjusting for age, gender, education, and diagnosis. These results support the use of the cSAA assay as a laboratory measure of anticholinergic burden.

Phytochemical Compounds and Pharmacological Activities of Vitis vinifera L.: An Updated Review

Grapes (Vitis vinifera L.) are commonly known grape species that belong to the Vitis genus in the Vitaceae family and come from western Asia and southern Europe. This review consists of traditional uses, phytochemical compounds, nutritional constituents, pharmacological activities, genotoxicological studies, and toxicity studies of V. vinifera. The data were obtained from scientific databases and search engines such as PubMed, Elsevier, Springer, Frontiers, Google Scholar, Scopus, Science Direct, and MDPI. In some countries, grapes used for traditional uses, such as drug therapy for blood-forming, anemia, allergies, wound care, colds and flu, carminative, bronchitis, diarrhea, and anti-phlegm. The main phytochemical compounds in V. vinifera are phenolic compounds, aromatic acids, flavonoids, proanthocyanidins, and stilbenoids. Nutritional constituents can be found in grapevines, i.e., proteins, lipids, carbohydrates, minerals, and vitamins. Parts of the grapevines had a wide variety of biological activities, i.e., antioxidant, antiviral, antiplatelet, antifungal, anticataract, antiobesity, anticholinergic, anti-sunburn, anti-inflammatory, and wound-healing activities. The phytochemical compounds content in each part of the grapevines were different. Each pharmacological activity depends on the grapevine's phytochemical compounds, components used, and extraction type. However, more studies are needed regarding the genotoxicity and toxicity of V. vinifera.

Anticholinergic Activity of Psychotropic Drugs and Cognitive Impairment Among Participants Aged 45 and Over: The CONSTANCES Study.

Psychotropic drugs such as anxiolytics, antidepressants and antipsychotics may have anticholinergic properties that could directly affect patients' cognition. Our objective was to assess the relationship between exposure to anticholinergic-positive (AC+) psychotropic drugs and cognitive impairment compared with psychotropic drugs without anticholinergic activity (AC-). This analysis included participants (aged 45-70 years) enrolled between January 2012 and October 2017 in the CONSTANCES cohort treated with psychotropic drugs (antidepressants n=2602, anxiolytics n=1195, antipsychotics n=197) in the 3 years preceding cognitive assessment. Within each drug class, the Anticholinergic Cognitive Burden scale was used to classify drugs as either AC+ or AC-. Cognitive impairment was defined as a score below - 1 standard deviation from the standardized mean of the neuropsychological score. We used multiple logistic regression models and matching on propensity score to estimate the relationship between anticholinergic activity and cognitive impairment. Our analyses did not show any increased risk of cognitive impairment for AC+ antidepressants and anxiolytics, with the exception of a slight increase for AC+ antidepressants in episodic memory (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.05-1.36). Conversely, we found a more marked increase in risk with AC+ antipsychotics on executive function (Trail Making Test-A [TMT-A], OR 4.49 [95% CI 2.59-7.97] and TMT-B, OR 3.62 [95% CI 2.25-5.89]). Our results suggest there is no clinically relevant association between the anticholinergic activity of antidepressant and anxiolytic drugs and cognitive impairment in middle-aged adults. An association could exist between AC+ antipsychotics and executive function.

Can the combined treatment of solifenacin and imipramine has a role in desmopressin refractory monosymptomatic nocturnal enuresis? A prospective double-blind randomized placebo-controlled study.

Nocturnal enuresis is a common disease of childhood. It can be classified into monosymptomatic nocturnal enuresis (MNE) or nonmonosymptomatic nocturnal enuresis (NMNE). Imipramine is a tricyclic antidepressant used to treat enuresis with initial success rates are high as 50% but some studies record a high relapse rate and it has a cardiotoxic effect when overdosed. Anticholinergics may be effective in the treatment of children with bladder storage dysfunction, including daytime incontinence. However, anticholinergics monotherapy is not effective in treating MNE. In our study, we used a low dose (25 mg) of imipramine in order to avoid its potential side effects and combined it with the synergistic anticholinergic action of solifenacin. Our objective was to evaluate the efficacy and safety of the combination of solifenacin and imipramine compared with placebo in the treatment of desmopressin refractory MNE. One hundred children aged 6 years or more with primary MNE unresponsive to desmopressin treatment were included. The children were randomly divided into two equal groups. Group A received imipramine 25 mg and solifenacin 5-10 mg oral tablets and group B received placebo once 1 h before bedtime for 3 months. The primary end point was to investigate the efficacy of the combined treatment of solifenacin and imipramine and the secondary end point was the safety of the drugs. Our study showed that the mean post treatment wet nights per month was significantly lesser in the treatment group than placebo group (p < 0.001) and cure rate was significantly higher in treatment group than placebo group (p < 0.001). The relapse rate was statistically significantly lower in treatment group than placebo group (p = 0.032). No significant side effects related to the drugs were reported. The combination treatment of solifenacin and imipramine is a useful and safe treatment for nocturnal enuresis after failure of everything else.

Bay Leaf (Laurus Nobilis L.) Incense Improved Scopolamine-Induced Amnesic Rats by Restoring Cholinergic Dysfunction and Brain Antioxidant Status

Bay leaf (Laurus nobilis L.) has been shown to possesses various biological activities such as wound healing activity, antioxidant activity, antibacterial activity, antiviral activity, immunostimulant activity, anticholinergic activity, antifungal activity, insect repellant activity, anticonvulsant activity, antimutagenic activity, and analgesic and anti-inflammatory activity. The present study aimed to investigate whether the bay leaf incense (BL) elicits the memory formation via the action on the cholinergic system using a scopolamine (Sco)-induced rat model. Rats were exposed to BL over 5 min in a smoking chamber apparatus once daily for 22 days, whereas memory impairment was induced by Sco (0.7 mg/kg), a muscarinic receptor antagonist, delivered 30 min before each behavioral test. The phytochemical composition of BL was achieved by gas chromatograph–mass spectrometry (GCMS). Behavioral effects in rats were assessed by Y-maze, radial arm maze (RAM), and novel object recognition (NOR) paradigms. Additionally, the acetylcholinesterase (AChE) activity and the oxidative stress markers in the rat hippocampus were also evaluated. Exposure to BL significantly ameliorated Sco-induced cognitive impairment and oxidative stress in the rat hippocampus. The obtained results suggested that BL-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic system and antioxidant activities.

Copper(II) complexes with meclofenamate ligands: Structure, interaction with DNA and albumins, antioxidant and anticholinergic activity

The interaction of copper(II) with the non-steroidal anti-inflammatory drug sodium meclofenamate (Na-mclf) in the presence or absence of the nitrogen-donor co-ligands pyridine (py) or 2,2′-bipyridylamine (bipyam), yielded the novel Cu(II) complexes [Cu2(mclf-O,O′)4(MeOH)2]·2MeOH (1·2MeOH), [Cu(mclf-O)2(py)3]·H2O·0.5MeOH (2·H2O·0.5MeOH) and [Cu(mclf-O,O′)2(bipyam)] (3). The characterization of the complexes was achieved by various techniques, including single-crystal X-ray crystallography. In order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA, various techniques were employed which suggested intercalation between the DNA-bases as the most possible interaction mode. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the EB from the EB-DNA adduct, verifying the intercalative binding mode. The affinity of the complexes to bovine and human serum albumin proteins (SAs) was investigated by fluorescence emission spectroscopy and the corresponding binding constants bear relatively high values, showing that the complexes bind tightly and possibly reversibly to SAs. The antioxidant activity of the complexes against 1,1-diphenyl-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and the ability to reduce H2O2 proved to be of significant magnitude. The in vitro inhibitory activity against the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was evaluated, in order to assess the anticholinergic ability of the complexes, which appeared promising.

Delirium due to Anticholinergic Drug Burden in Older Persons

The cumulative effect of medications with anticholinergic activity (known as Anticholinergic Drug Burden, ADB) is associated with incident delirium and onset of adverse outcomes in older persons (e.g., cognitive and functional impairment). In a recent study by Egberts and colleagues, the association between delirium and ADB was demonstrated, mainly when assessed using the Anticholinergic Risk Scale (ARS). Although drugs with anticholinergic properties are often included in lists of potentially inappropriate medications, their prescription is still widespread. More efforts should be made to support deprescribing strategies and limit the prescription of potentially harmful medications.

New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors

A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π–π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π–π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.