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Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase
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Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase
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Journal Article
Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase
2016
Overview
Three patients had severe ataxia and memory impairment in a phase 1 trial of a fatty acid amide hydrolase inhibitor designed as an analgesic and antiinflammatory drug. One patient became brain dead. MRI of the brain showed lesions in the pons and hippocampi.
A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids.
1
FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models,
2
and some have been tested for these purposes in phase 1 and phase 2 studies.
3
Phase 3 studies were not pursued owing to a lack of efficacy. BIA 10-2474, with the chemical name 3-(1-(cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide, is a new reversible FAAH inhibitor. A phase 1 study was conducted in healthy volunteers to explore the safety profile of BIA 10-2474. Five of the six participants who had received the highest cumulative dose . . .
Publisher
Massachusetts Medical Society
Subject
/ Adult
/ Amidohydrolases - antagonists & inhibitors
/ Cerebellar Diseases - chemically induced
/ Cerebral Hemorrhage - chemically induced
/ Cerebral Hemorrhage - diagnosis
/ Consciousness Disorders - chemically induced
/ Cyclic N-Oxides - administration & dosage
/ Cyclic N-Oxides - adverse effects
/ Enzymes
/ Gait Ataxia - chemically induced
/ Headache
/ Headache - chemically induced
/ Humans
/ Male
/ Memory
/ Memory Disorders - chemically induced
/ Patients
/ Pons
/ Psychiatrics and mental health
/ Pyridines - administration & dosage
/ Toxicity
