Drug therapies for stroke and traumatic brain injury often display U-shaped dose responses: occurrence, mechanisms, and clinical implications.

Abstract:

:This article explores the occurrence of U-shaped dose responses induced by neuroprotective agents in animal stroke and traumatic brain injury (TBI) screening/preclinical studies. The assessment was stimulated by suggestions that U-shaped dose responses may be common for neuroprotective agents in stroke and TBI models, and its lack of both recognition and understanding may be a factor contributing to the failure of many promising drugs to be protective in clinical trials. Over 30 agents with neuroprotective properties in animal stroke/TBI models were identified that act via U-shaped dose responses in a broad range of experimental protocols. These findings suggest that U-shaped dose responses in animal stroke/TBI models may be a general occurrence and have significant implications for drug discovery, drug development, and clinical practice.

journal_name

Crit Rev Toxicol

authors

Calabrese EJ

doi

10.1080/10408440802014287

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

557-77

issue

6

eissn

1040-8444

issn

1547-6898

pii

794862548

journal_volume

38

pub_type

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