Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG

Borghans, Laura; Blokland, Arjan; Sambeth, Anke

doi:10.1007/s00213-017-4549-1

Cited by 9 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The findings regarding the biperiden-induced memory impairment found in this study are in line with the results from other studies (Borghans et al 2017; Sambeth et al 2015). In the study of Sambeth et al (2015), biperiden impaired recall on the immediate and delayed VLT and impaired accuracy on the SMT.…”

Section: Discussionsupporting

confidence: 94%

“…In the study of Sambeth et al (2015), biperiden impaired recall on the immediate and delayed VLT and impaired accuracy on the SMT. In the study of Borghans et al (2017), only the delayed recall of the VLT was impaired after biperiden. Furthermore, this study again conforms that biperiden is specific to episodic memory, as the results only show significant effects on measures of episodic verbal memory.…”

Section: Discussionmentioning

confidence: 87%

“…In this study, a dose of 2 mg was used, a dose well within the range of the recommended doses for biperiden. Furthermore, research has found that an oral dose of 2 mg impaired cognitive performance in healthy adults (Borghans et al 2017; McShane et al 2006; Sambeth et al 2015; Wezenberg et al 2005). …”

Section: Methodsmentioning

confidence: 99%

“…Biperiden has been found to reliably induce a memory deficit in healthy volunteers (Borghans et al 2017; Sambeth et al 2015; Wezenberg et al 2005). In contrast to the well-known scopolamine model (Ebert and Kirch 1998; Klinkenberg and Blokland 2010), biperiden is a selective muscarinic M1/M4 receptor antagonist.…”

Section: Introductionmentioning

confidence: 99%

“…To investigate the cognition-enhancing effects of riociguat in healthy young volunteers, the same cholinergic deficit model was applied as in the animal study. Biperiden has been found to reliably induce a memory deficit in healthy volunteers (Borghans et al 2017 ; Sambeth et al 2015 ; Wezenberg et al 2005 ). In contrast to the well-known scopolamine model (Ebert and Kirch 1998 ; Klinkenberg and Blokland 2010 ), biperiden is a selective muscarinic M1/M4 receptor antagonist.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a biperiden-induced memory impairment

et al. 2018

Self Cite

View full text Add to dashboard Cite

RationaleAfter stimulation with nitric oxide, soluble guanylate cyclase (sGC) produces cyclic guanosine monophosphate (cGMP), which stimulates an important signalling pathway for long-term potentiation (LTP). By upregulating cGMP, LTP could be stimulated and thereby enhancing memory processes. The present study investigated the effects of the sGC stimulator riociguat on cognition in healthy volunteers. Participants were pre-treated with and without biperiden, which impairs memory performance, to investigate the memory-enhancing effects of riociguat.MethodsTwenty volunteers participated in a double-blind placebo-controlled six-way crossover design with a cognitive test battery including the verbal learning task (VLT), n-back task, spatial memory test, the attention network test, and a reaction time task. Treatments were placebo and riociguat 0.5 mg, placebo and riociguat 1.0 mg, biperiden 2.0 mg and placebo, biperiden 2.0 mg and riociguat 0.5 mg and biperiden 2.0 mg and riociguat 1.0 mg.ResultsBlood pressure was found to be decreased and heart rate to be increased after administration of riociguat. Cognitive performance was not enhanced after administration of riociguat. Biperiden decreased episodic memory on the VLT, yet this deficit was not reversed by riociguat.ConclusionThis supports the notion that biperiden might be a valuable pharmacological model to induce episodic memory impairments as observed in AD/MCI.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a biperiden-induced memory impairment

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

The antimuscarinic agent biperiden selectively impairs recognition of abstract figures without affecting the processing of non‐words

Toth

Sambeth

Blokland

2021

Human Psychopharmacology

Self Cite

View full text Add to dashboard Cite

Objectives The present study investigated the effects of biperiden, a muscarinic type 1 antagonist, on the recognition performance of pre‐experimentally unfamiliar abstract figures and non‐words in healthy young volunteers. The aim was to examine whether 4 mg biperiden could model the recognition memory impairment seen in healthy aging. Methods A double‐blind, placebo‐controlled, two‐way crossover study was conducted. We used a three‐phase (deep memorization, shallow memorization, and recognition) old/new discrimination paradigm in which memory strength was manipulated. Strong memories were induced by deep encoding and repetition. Deep encoding was encouraged by redrawing the abstract figures and mentioning existing rhyme words for the non‐words (semantic processing). Weak memories were created by merely instructing the participants to study the stimuli (shallow memorization). Results Biperiden impaired recognition accuracy and prolonged reaction times of the drawn and the studied abstract figures. However, participants were biased towards “old” responses in the placebo condition. The recognition of the new abstract figures was unaffected by the drug. Biperiden did not affect the recognition of the non‐words. Conclusions Although biperiden may model age‐related deficits in episodic memory, the current findings indicate that biperiden does not mimic age‐related deficits in recognition performance.

show abstract

Biperiden Challenge Model in Healthy Elderly as Proof‐of‐Pharmacology Tool: A Randomized, Placebo‐Controlled Trial

Bakker

Esdonk

Stuurman

et al. 2021

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Selective M 1 muscarinic acetylcholine receptor (mAChR) agonists are being developed as symptomatic treatment for neurodegenerative and neuropsychiatric disorders that lead to cognitive dysfunction. Demonstrating cognition enhancing effects in early phase clinical development in healthy subjects is difficult. A challenge with the M 1 mAChR antagonist biperiden could be used to demonstrate procognitive and pharmacological effects of selective M 1 mAChR agonists. The aim of this study was to develop such a model. To this end, twelve healthy elderly subjects participated in a randomized, placebo controlled, three-way crossover study investigating tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of 2 and 4 mg biperiden. Repeated PD assessments were performed using neurocognitive tasks and electrophysiological measurements. A population PK-PD model was developed. Four mg biperiden showed significant impairment of sustained attention (-2.1% point in adaptive tracking (95% CI [-3.043; -1.148])), verbal memory (2-3 words fewer recalled (95% CI [-5.9; -0.2])), and working memory (up to 50 ms increase in the n-back task reaction time (95% CI [21.854; 77.882])) compared with placebo. The PK data was best fitted by a 2-compartment model and showed a high inter-occasion and inter-subject variability. Population PK-PD analysis quantified significant concentration-effect relationships for the n-back reaction times, n-back accuracies and adaptive tracking. In conclusion, biperiden caused M 1 mAChR related doseand concentration-dependent temporary declines in cognitive functioning. Therefore a biperiden pharmacological challenge model can be used for proof-of-pharmacology studies and to demonstrate cognition enhancing effects of new cholinergic compounds that are being developed.

show abstract

Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG

Cited by 9 publications

References 36 publications

The effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a biperiden-induced memory impairment

The effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a biperiden-induced memory impairment

The antimuscarinic agent biperiden selectively impairs recognition of abstract figures without affecting the processing of non‐words

Biperiden Challenge Model in Healthy Elderly as Proof‐of‐Pharmacology Tool: A Randomized, Placebo‐Controlled Trial

Contact Info

Product

Resources

About