The objective of this study is to test the experimental reproducibility and within-subject variability of qEEG (quantitative electroencephalogram) using two probe compounds: MK3134 and lorazepam.
This study will test the hypothesis that EEG (Electroencephalogram) theta power, averaged across a topographical region of interest is decreased 6 hours after administration of MK3134 compared to placebo.
The objective of this study is to test the experimental reproducibility and within-subject variability of qEEG using two probe compounds: MK3134 and lorazepam.

Start Date01 Jun 2010

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT00887601 / CompletedPhase 1

A 4-Period, Placebo-Controlled, Crossover Study to Evaluate the Utility and Feasibility of BOLD fMRI and Cerebral Blood Flow Measurements as Biomarkers for Cognition Enhancing Drugs (Donepezil and MK3134)

This study will evaluate functional magnetic resonance imaging (fMRI) and methods for measuring drug induced changes in cerebral blood flow as biomarkers for attention-improving drugs.

Start Date01 Aug 2007

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT01181310 / CompletedPhase 1

A Five-Period, Placebo-Controlled, Crossover Study to Evaluate the Effect of Donepezil and MK-3134 on Reversal of Cognitive Impairment Associated With a Single-Dose of Scopolamine.

The drug, scopolamine, can result in short-term impairments of cognitive function, attention, and memory that resemble those seen in aging and Alzheimer's disease. This study tested the capability of both individual and combined doses of MK-3134 and the current standard treatment: donepezil (Aricept), to reverse such impairments, following a single dose of scopolamine. Participants were evaluated after each of 5 different treatment periods (in a cross-over, double-dummy design): A: placebo to match both donepezil (oral [PO]) and MK-3134 (PO) followed by placebo scopolamine (subcutaneous [SQ]); B: placebo to match both donepezil (PO) and MK-3134 (PO), followed by scopolamine SQ; C: MK-3134 (PO) followed by scopolamine SQ; D: donepezil (PO) followed by scopolamine SQ; E: MK-3134 (PO) and donepezil (PO) followed by scopolamine SQ. The doses of MK3134, donepezil, and scopolamine were the same over all treatment arms in which the specified drug was administered. There were 8 total visits for each treatment period, including 5 Treatment Visits requiring 14-day intervals between visits for study-drug washout. Participants were assessed for cognitive function before and after each treatment period during the Treatment Visits.

Start Date01 Jun 2007

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with MK-3134

100 Translational Medicine associated with MK-3134

100 Patents (Medical) associated with MK-3134

Literatures (Medical) associated with MK-3134

01 Jan 2014·Journal of Nuclear MedicineQ1 · MEDICINE

¹¹C-MK-8278 PET as a Tool for Pharmacodynamic Brain Occupancy of Histamine 3 Receptor Inverse Agonists

Q1 · MEDICINE

Article

Author: de Hoon, Jan ; Han, Lingling ; Iannone, Robert ; Van Laere, Koenraad J. ; Koole, Michel ; Mozley, David P. ; Cerchio, Kristine ; Bormans, Guy ; Van Hecken, Anne ; Plalcza, John ; Burns, Donald H. ; Renger, John ; Hamill, Terence G. ; Hargreaves, Richard J. ; Sanabria-Bohrquez, Sandra M. ; Depre, Marleen ; De Lepeleire, Inge

The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity.METHODSUsing PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level.RESULTSThe mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses.CONCLUSION(11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

01 Dec 2011·PsychopharmacologyQ3 · MEDICINE

Additive effects of a cholinesterase inhibitor and a histamine inverse agonist on scopolamine deficits in humans

Q3 · MEDICINE

Article

Author: John Renger ; John Connell ; Cindy Gargano ; Ajay Verma ; Paul Maruff ; Nicole Calder ; Sabrina Fox-Bosetti ; Gary Herman ; Christopher Lines ; Aizza Hassan ; Scott Doran ; William Cho

RATIONALEEnhancement of histaminergic neurotransmission or histaminergic plus cholinergic neurotransmission may represent novel strategies for improving cognition in Alzheimer's disease.OBJECTIVETo evaluate the effects of a novel histamine H3 receptor inverse agonist (MK-3134), an acetylcholinesterase inhibitor (donepezil), and their combination in attenuating the cognitive impairment associated with scopolamine.METHODSThirty-one subjects were randomized, and 28 completed this double-blind, placebo-controlled, five-period crossover study. Cognition was assessed using the Groton Maze Learning Task (GMLT) as the primary outcome measure. The two primary hypotheses were that donepezil 10 mg and MK-3134 25 mg, respectively, would attenuate scopolamine (0.5 mg)-induced impairment as measured by the GMLT over the first 12 h after scopolamine administration (AUC(1-12) (h)). A secondary hypothesis was that the combination of donepezil and MK-3134 would attenuate scopolamine-induced cognitive impairment to a greater extent than either agent alone as measured by the GMLT AUC(1-12 h).RESULTSThe primary and secondary hypotheses were not met. Upon examining the time course of the scopolamine effects (an exploratory objective), peak effects were generally observed around 2 h after scopolamine administration. Administration of MK-3134 or donepezil improved performance on the GMLT at the 2-h time point, rather than AUC(1-12 h), compared with scopolamine alone. Moreover, it appeared that the combination of MK-3134 and donepezil blunted the scopolamine effect to a greater extent than either drug alone.CONCLUSIONSExploratory analyses provide evidence for cognitive improvement through inverse agonism of the H3 histamine receptor and for cooperation between human cholinergic and histaminergic neurotransmitter systems. (ClinicalTrials.gov trial registration number: NCT01181310).

100 Deals associated with MK-3134

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Cognitive Dysfunction	Phase 1	-	Merck Sharp & Dohme Corp.	01 Jun 2007
Dementia	Phase 1	GB	Merck GmbH	-
Dementia	Phase 1	BE	Merck GmbH	-

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