PMID- 2213560
OWN - NLM
STAT- MEDLINE
DCOM- 19901121
LR  - 20071115
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 255
IP  - 1
DP  - 1990 Oct
TI  - Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) 
      interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist.
PG  - 256-63
AB  - BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its 
      capacity to block PAF, endotoxin and recombinant human tumor necrosis 
      factor-alpha (rTNF)-mediated effects. In vitro, BN 50739 blocked PAF-induced 
      platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), 
      respectively. In the conscious rat, pretreatment (30 min) with BN 50739 (n = 
      5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs. - 43 +/- 
      2 mm Hg, P less than .01) and shortened the recovery time of mean arterial 
      pressure (22 +/- 13 vs. 325 +/- 46 sec, P less than .01). BN 50739 (10 mg/kg 
      i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 
      +/- 1 vs. 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs. 60%, P 
      less than .05). Only partial protection was conveyed by BN 50739 against the 
      hypotensive response to endotoxin (115 +/- 3 vs. 91 +/- 4 mm Hg, P less than 
      .03). Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of 
      plasma thromboxane B2 (21.2 +/- 0.8 vs. 46.7 +/- 11.8 pg/100 microliters, P less 
      than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs. 26,430 +/- 3541 
      U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained 
      unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Rabinovici, R
AU  - Rabinovici R
AD  - Department of Pharmacology, Smithkline Beecham Laboratories, King of Prussia, 
      Pennsylvania.
FAU - Yue, T L
AU  - Yue TL
FAU - Farhat, M
AU  - Farhat M
FAU - Smith, E F 3rd
AU  - Smith EF 3rd
FAU - Esser, K M
AU  - Esser KM
FAU - Slivjak, M
AU  - Slivjak M
FAU - Feuerstein, G
AU  - Feuerstein G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Azepines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thromboxanes)
RN  - 0 (Triazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 128672-07-1 (BN 50739)
SB  - IM
MH  - Animals
MH  - Azepines/*pharmacology
MH  - Blood Cells/drug effects
MH  - Hemodynamics/drug effects
MH  - Humans
MH  - Lipopolysaccharides/toxicity
MH  - Male
MH  - Platelet Activating Factor/*antagonists & inhibitors/biosynthesis
MH  - Platelet Aggregation/drug effects
MH  - Platelet Aggregation Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Recombinant Proteins/pharmacology
MH  - Shock, Septic/metabolism/*prevention & control
MH  - Thromboxanes/metabolism
MH  - Triazoles/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*analysis/pharmacology
EDAT- 1990/10/01 00:00
MHDA- 1990/10/01 00:01
CRDT- 1990/10/01 00:00
PHST- 1990/10/01 00:00 [pubmed]
PHST- 1990/10/01 00:01 [medline]
PHST- 1990/10/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1990 Oct;255(1):256-63.