Cortical excitability threshold can be increased by the AMPA blocker Perampanel in amyotrophic lateral sclerosis.
Muscle Nerve
; 64(2): 215-219, 2021 08.
Article
in English
| MEDLINE | ID: covidwho-1245512
ABSTRACT
INTRODUCTION/AIMS:
Cortical hyperexcitability is a feature of amyotrophic lateral sclerosis (ALS) and cortical excitability can be measured using transcranial magnetic stimulation (TMS). Resting motor threshold (MT) is a measure of cortical excitability, largely driven by glutamate. Perampanel, a glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker, is predicted to increase the cortical excitability threshold. This study aimed to evaluate TMS to functionally assess target engagement in a study of perampanel in ALS.METHOD:
We studied the MT of ALS patients randomized to a single dose of perampanel or placebo 51 hourly for 4 h. Twelve patients participated at 4 mg and 7 returned for dosing and retesting at 8 mg. The study was terminated in April 2020 due to coronavirus disease 2019-related restrictions, after 7 out of 12 planned patients had received the 8 mg dose. Serum concentrations were also measured.RESULTS:
Ten patients received the 4 mg dose (2 received placebo) and 5 received the 8 mg dose (2 received placebo). Motor Threshold increased at 2 h after dosing in the combined treatment group +7% of maximal stimulator output (P < .01). Change could be detected in the larger 4 mg group (P = .02), but not in the smaller 8 mg dose group (P = .1). No side effects were reported after single dose exposure.DISCUSSION:
This study shows that perampanel effects the physiology of upper motor neurons. Studies aiming at gauging the effect of perampanel on ALS disease progression are already ongoing. Motor threshold may serve as a marker of biological target engagement.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pyridones
/
Receptors, AMPA
/
Cortical Excitability
/
Amyotrophic Lateral Sclerosis
/
Motor Neurons
Type of study:
Diagnostic study
/
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
Muscle Nerve
Year:
2021
Document Type:
Article
Affiliation country:
Mus.27328
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