A calcium fluorescence assay for quantification of cholinergic receptor activity of clinical drugs in serum - comparison with radioactive methods.

Published on Sep 2, 2021in Journal of Pharmacological and Toxicological Methods1.95
· DOI :10.1016/J.VASCN.2021.107118
José N. Nobrega50
Estimated H-index: 50
(U of T: University of Toronto),
Roger Raymond19
Estimated H-index: 19
(CAMH: Centre for Addiction and Mental Health)
+ 1 AuthorsBruce G. Pollock89
Estimated H-index: 89
(U of T: University of Toronto)
Abstract null null A new approach is described for quantifying cholinergic receptor activation status human blood samples, based on M1 receptor-driven mobilization of intracellular calcium stores. The assay identifies anticholinergic as well as agonist cholinergic receptor activity. As a cell-based procedure, the assay shares the high efficiency of recently developed M1 receptor binding protocols, but differs from the latter in relying on fluorescence rather than radioactivity measurements. The assay targets a true functional effect insofar as it reflects a time-dependent process of net changes in activation of cholinergic receptors. Results from experiments with M1-expressing CHO cells exposed to a fluorogenic dye and the standard cholinergic agonist carbachol revealed the assay's ability to isolate pure agonist effects of clinical compounds as well as the net effects of serum containing agonist and antagonist factors. The new protocol thus provides two additional quantitative indices of cholinergic receptor activity in human serum, namely pure agonistic effects and net agonist/antagonist effects. As such, it could constitute a very useful addition to efforts to quantify global cholinergic status in human serum in various clinical conditions. By relying on fluorescence measures it should also prove much more accessible than radioactivity-based protocols.
📖 Papers frequently viewed together
#1Yash B. JoshiH-Index: 18
#2Michael L. ThomasH-Index: 24
Last. Laura C. LazzeroniH-Index: 43
view all 22 authors...
Objective Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients...
#1Susmita Chandramouleeshwaran (CAMH: Centre for Addiction and Mental Health)H-Index: 1
#2Naba Ahsan (CAMH: Centre for Addiction and Mental Health)H-Index: 2
Last. Tarek K. Rajji (U of T: University of Toronto)H-Index: 48
view all 14 authors...
ABSTRACT Objectives 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. Design The study was...
#1José N. NobregaH-Index: 50
#2Roger Raymond (CAMH: Centre for Addiction and Mental Health)H-Index: 19
Last. Bruce G. Pollock (CAMH: Centre for Addiction and Mental Health)H-Index: 18
view all 3 authors...
Abstract Assessments of total anticholinergic activity (SAA) in serum are of considerable interest for its potential involvement in cognitive impairment associated with polydrug states in the elderly and other populations. Such estimations have been based on the displacement of radioligand binding in rat brain tissues. The validity of such measurements has been questioned, as a potentially distorting effect of large serum proteins was identified. We sought to develop a modified assay that would ...
#1Karen Cardwell ('QUB': Queen's University Belfast)H-Index: 7
#2Carmel M. Hughes ('QUB': Queen's University Belfast)H-Index: 59
Last. Cristín Ryan ('QUB': Queen's University Belfast)H-Index: 28
view all 3 authors...
Background Increased exposure to anticholinergic medication is problematic, particularly in those aged 80 years and older.
#1Tarek K. RajjiH-Index: 48
#2Benoit H. MulsantH-Index: 95
Last. Gary RemingtonH-Index: 85
view all 7 authors...
Objective:Clozapine’s potent antagonism of muscarinic M1 receptors is thought to worsen working memory deficits associated with schizophrenia. In contrast, its major metabolite, N-desmethylclozapine (NDMC), is thought to enhance working memory via its M1 receptor agonist activity. The authors hypothesized that the ratio of serum clozapine and NDMC concentrations would be inversely associated with working memory performance in schizophrenia.Method:Thirty patients with schizophrenia or schizoaffec...
#1Pasi Lampela (University of Eastern Finland)H-Index: 11
#2Piia Lavikainen (University of Eastern Finland)H-Index: 19
Last. Sirpa Hartikainen (University of Eastern Finland)H-Index: 53
view all 6 authors...
Background The serum anticholinergic activity (SAA) assay has been used to quantify patients’ anticholinergic load. In addition, several ranked lists of anticholinergic drugs have been developed to assess anticholinergic drug burden.
#1Noll L. CampbellH-Index: 25
#2Anthony J. Perkins (IU: Indiana University)H-Index: 21
Last. Malaz Boustani (IU: Indiana University)H-Index: 67
view all 5 authors...
Objectives: To describe the association between anticholinergic medications and incident delirium in hospitalized older adults with cognitive impairment and to test the hypothesis that anticholinergic medications would increase the risk of incident delirium. Design: Observational cohort study. Setting: Urban public hospital in Indianapolis, Indiana. Participants: One hundred forty-seven participants aged 65 and older with cognitive impairment who screened negative for delirium at the time of adm...
#1Philip Gerretsen (CAMH: Centre for Addiction and Mental Health)H-Index: 24
#2Bruce G. Pollock (U of T: University of Toronto)H-Index: 89
Introduction: Many commonly used drugs have primary or secondary anticholinergic effects contributing to adverse outcomes ranging from mild-to-severe to potentially lethal. Anticholinergic adverse effects frequently occur with medications prescribed with other intended mechanisms of action, including antihistamines, antidepressants, and antipsychotics. Anticholinergic drugs are also the principal treatments of clinical conditions, such as urinary incontinence, that tend to occur in the elderly. ...
#1Shigeyuki Yamamoto (Hamamatsu University)H-Index: 10
#2Shingo NishiyamaH-Index: 34
Last. Edward F. DominoH-Index: 67
view all 8 authors...
The muscarinic cholinergic receptor (mAChR) antagonist scopolamine was used to induce transient cognitive impairment in monkeys trained in a delayed matching to sample task. The temporal relationship between the occupancy level of central mAChRs and cognitive impairment was determined. Three conscious monkeys (Macaca mulatta) were subjected to positron emission tomography (PET) scans with the mAChR radioligand N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB). The scan sequence was pre-, 2, 6,...
#1Konstanze Plaschke (Heidelberg University)H-Index: 23
#2Jürgen KopitzH-Index: 46
Last. Peter TeschendorfH-Index: 15
view all 5 authors...
Increased patients' serum anticholinergic activity (SAA) is described as a marker of cognitive dysfunction and can be influenced by different exogenous and endogenous factors. The role of cortisol in relation to SAA and cognition in perioperative conditions has not been investigated so far. In 30 men scheduled for urological surgery, the authors determined SAA and cortisol levels in blood and CSF and conducted neuropsychological testing in two subgroups with comparable pre- and intraoperative ch...
Cited By0
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.