Delinquents and the tapping test

Andrew, June M.

doi:10.1002/1097-4679(197707)33:3<786::aid-jclp2270330340>3.0.co;2-x

Cited by 16 publications

(10 citation statements)

References 21 publications

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“…The “NeuroCart” is a battery of sensitive tests for a wide range of CNS domains that was developed to examine different kinds of CNS-active drugs [20] . The N-back test and the digit symbol substitution test were used to evaluate working memory [21] , [22] , [23] , [24] , [25] , [26] ; the Stroop test evaluated inhibition, interference, and controlled versus automatic processing [27] ; adaptive tracking measured attention and eye-hand coordination [28] , [29] , [30] , [31] , [32] , [33] ; the single reaction time task measured reaction time [34] ; finger tapping measured motor speed [35] ; the Visual Analogue Scale according to Bond & Lader was used to assess subjective states [36] , [37] ; pharmaco-electroencephalography, eye movements, and pupil size were used to monitor any drug effects, which can be interpreted as evidence of penetration and activity in the brain [32] , [33] , [38] , [39] ; body movements were measured with the body sway meter [40] ; and the Visual Verbal Learning Test (VVLT) measured the whole scope of learning behavior (i.e., acquisition, consolidation, storage, and retrieval) [41] .…”

Section: Methodsmentioning

confidence: 99%

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

Baakman

Álvarez-Jiménez

Loewen³

et al. 2019

A&D Transl Res & Clin Interv

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Introduction Donepezil is a widely used cholinesterase inhibitor in the management of Alzheimer's disease. Despite large-scaled evidence for its efficacy, elevated peripheral ACh levels often lead to side effects and are dose limiting. The present exploratory study is designed to determine the potentiation of the effects of donepezil by cotreatment with EVP-6124, an alpha-7 nicotinic agonist, to reduce scopolamine-induced cognitive deficits in healthy elderly subjects. Secondary objectives are to explore safety and pharmacokinetic and pharmacodynamics effects of EVP-6124 alone and in combination with donepezil compared to placebo. Methods A phase I randomized, single-center, placebo-controlled, double-blind, five-way, partial crossover study was performed with donepezil 2.5, 5 mg or placebo combined with EVP-6124 0.3, 1, 2, 4 mg or placebo in three cohorts of healthy elderly subjects in a scopolamine (0.3 mg i.v.) challenge test. Safety, pharmacokinetic, and pharmacodynamics outcomes were assessed. Results A total of 36 subjects completed the study. Donepezil pharmacokinetic parameters were similar with and without EVP-6124. Effective dose combinations were donepezil/EVP-6124(5/2 mg) and donepezil/EVP-6124 (5/0.3 mg) and showed improvements of the delayed recall of the Visual Verbal Learning Test (1.2; CI = 0.1–2.3) and reaction time during the two-back condition of the N-back (−42; CI = −77, −8), respectively. Overall, no marked reversal of scopolamine effects was observed. Discussion This study shows no synergistic effect of subtherapeutic doses of donepezil and EVP-6124 in a scopolamine challenge model in healthy elderly subjects. Dosing of scopolamine and the combination of donepezil and EVP-6124 requires further study.

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Section: Methodsmentioning

confidence: 99%

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

Baakman

Álvarez-Jiménez

Loewen³

et al. 2019

A&D Transl Res & Clin Interv

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“…The dominant hand finger tapping test was performed to evaluate motor activation and fluency . The volunteer was instructed to tap as quickly as possible with the index finger of the dominant hand.…”

Section: Methodsmentioning

confidence: 99%

Reversal of mecamylamine‐induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses

Álvarez-Jiménez

Hart

Prins

et al. 2018

Brit J Clinical Pharma

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“…The finger tapping test was adapted from the Halstead Reitan Test Battery [45]. The test evaluates motor activation and fluency.…”

Section: Methodsmentioning

confidence: 99%

Central nervous system effects of the interaction between risperidone (single dose) and the 5‐HT₆ antagonist SB742457 (repeated doses) in healthy men

Liem-Moolenaar

Rad

Zamuner³

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Several lines of evidence suggest a possible role of 5-HT6 receptor antagonists in dementia or cognitive dysfunction of schizophrenia. SB-742457 is a potent 5-HT6 antagonist and has shown efficacy in different animal models of cognitive impairment. It is currently in development as a cognitive enhancer. Risperidone, commonly used to control agitation and psychotic features in both schizophrenia and Alzheimer's disease, is a D 2 /5-HT2A antagonist with low affinity for 5-HT6 receptors and limited effects on cognitive parameters. WHAT THIS STUDY ADDS• As the combination of risperidone and SB-742457 may constitute a reasonable combination in cognitively impaired patients, pharmacodynamic interaction effects were investigated in this study.The only significant drug-drug interaction was a small increase of electroencephalogram (EEG) alpha and beta bands, which might suggest mild arousing activity of SB-742457 on the central nervous system-depressant effects of risperidone.The clinical relevance of these findings in patients remains to be established. Additionally, this study provided an extensive multidimensional pharmacodynamic profile of risperidone in healthy volunteers, showing that this antipsychotic suppresses motor performance (eye-hand coordination, finger tapping and postural stability), alertness, memory and neurophysiological functions (saccadic eye movements and EEG power spectrum). AIMSeveral lines of evidence suggest a possible role of 5-HT6 receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders.Therefore, the pharmacological interactions between the 5-HT6 antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODSA randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTSTreatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P = 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P = 0.016). No significant effects of SB-742457 alone were found. CONCLUSIONThe pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone...

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Delinquents and the tapping test

Cited by 16 publications

References 21 publications

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

Reversal of mecamylamine‐induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses

Central nervous system effects of the interaction between risperidone (single dose) and the 5‐HT₆ antagonist SB742457 (repeated doses) in healthy men

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Delinquents and the tapping test

Cited by 16 publications

References 21 publications

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

Reversal of mecamylamine‐induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses

Central nervous system effects of the interaction between risperidone (single dose) and the 5‐HT6 antagonist SB742457 (repeated doses) in healthy men

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Product

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Central nervous system effects of the interaction between risperidone (single dose) and the 5‐HT₆ antagonist SB742457 (repeated doses) in healthy men