Document Detail


Pharmacological models in healthy volunteers: their use in the clinical development of psychotropic drugs.
MedLine Citation:
PMID:  17591655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Animal models of diseases are widely used in the preclinical phase of drug development. They have a place in early human clinical psychopharmacology as well, in order to get early clues that contribute to establish the proof of concept (POC) already in healthy volunteers (HV). Different types of models are available (pharmacological or non-pharmacological provocation, models based on age-related characteristics). This review is focused on pharmacological models in HV, with the aim to identify the main issues raised by their use in pharmaceutical trials. The available models unevenly fulfil the requirements of face validity, sufficient response rate, test-retest consistence and responsiveness to reference drugs. Most of them have been developed in the purpose of pathophysiology studies, using rating instruments validated for clinical practice. Substantial progress could be made by adapting models to the specific requirements of pharmaceutical trials, including wider use of biomarkers. Characteristics that make models, as well as biomarkers, suitabLe for use in drug development are proposed. Despite obvious limitations, human models can significantly enhance the way phase I studies contribute to establish the POC, provided they are integrated into adapted phase I development plans. Their use as industrial tools for drug evaluation requires specific, dedicated development.
Authors:
Christian Gilles; Remy Luthringer
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of psychopharmacology (Oxford, England)     Volume:  21     ISSN:  0269-8811     ISO Abbreviation:  J. Psychopharmacol. (Oxford)     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-06-26     Completed Date:  2007-08-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8907828     Medline TA:  J Psychopharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  272-82     Citation Subset:  IM    
Affiliation:
Centre Hospitalier de l'Ardenne, Sainte Ode, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Apomorphine / pharmacology
Cognition Disorders / chemically induced,  psychology
Dopamine Agonists / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
GABA Modulators / pharmacology
Humans
Ketamine / pharmacology
Lorazepam / pharmacology
Memory Disorders / chemically induced,  psychology
Models, Psychological
Muscarinic Antagonists / pharmacology
Panic Disorder / chemically induced,  drug therapy,  physiopathology
Psychotropic Drugs / pharmacology*
Scopolamine / pharmacology
Tryptophan / deficiency,  physiology
Chemical
Reg. No./Substance:
0/Dopamine Agonists; 0/Excitatory Amino Acid Antagonists; 0/GABA Modulators; 0/Muscarinic Antagonists; 0/Psychotropic Drugs; 51-34-3/Scopolamine; 58-00-4/Apomorphine; 6740-88-1/Ketamine; 73-22-3/Tryptophan; 846-49-1/Lorazepam

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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