Document Detail


BMS-181168 for protection of the human brain against hypoxia: double-blind, placebo-controlled EEG mapping studies.
MedLine Citation:
PMID:  7838889     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In a double-blind, placebo-controlled, cross-over trial, the antihypoxidotic properties of BMS-181168 (previously BMY 21502)--a 1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-2- pyrrolidinone alleviating impairment of learning and memory in the animal--were studied utilizing EEG mapping under an experimental hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found at 6000 m altitude), which was inhaled for 23 minutes under normobaric conditions by 16 healthy male volunteers (aged 23-35 years, mean 27.2 years). After an adaptation session, they received in randomized order at weekly intervals oral single doses of placebo, or of 100 mg, 200 mg, and 400 mg BMS-181168. Evaluation of blood gases (PO2, PCO2, SO2), adverse events, and EEG mapping was carried out prior to drug administration and 2, 4, 6 and 8 hours post-drug, on each occasion under normoxic and transient hypoxic conditions. Hypoxemia was controlled by drawing arterialized capillary blood samples from the earlobes after hyperemization of the latter (after 0, 14, and 23 minutes of hypoxic gas inhalation) and by oximetry. After 23 minutes of inhalation, analysis showed a drop in PO2 from 98 to 48 mm Hg, in PCO2 from 41 to 31 mm Hg, and in SO2 from 97 to 80%. Descriptive statistical analyses of EEG mapping data demonstrated under hypoxia/placebo conditions an increase in delta/theta activity and a decrease in alpha activity as well as a slowing of the delta/theta centroid and an increase in the alpha and beta centroid, which suggests a marked deterioration in physiological vigilance.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
B Saletu; H Schulz; W M Herrmann; P Anderer; R C Shrotriya; E Vanbrabant
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Pharmacopsychiatry     Volume:  27     ISSN:  0176-3679     ISO Abbreviation:  Pharmacopsychiatry     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1995-02-28     Completed Date:  1995-02-28     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8402938     Medline TA:  Pharmacopsychiatry     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  189-97     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, School of Medicine, University of Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adult
Analysis of Variance
Arousal / drug effects
Blood Gas Analysis
Brain Mapping*
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Electroencephalography / drug effects*
Humans
Hypoxia, Brain / physiopathology,  prevention & control*
Male
Psychotropic Drugs / pharmacology*
Pyrimidines / pharmacology*
Pyrrolidinones / pharmacology*
Chemical
Reg. No./Substance:
0/Psychotropic Drugs; 0/Pyrimidines; 0/Pyrrolidinones; 123259-91-6/BMY 21502

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


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