Biological properties of the antagonist SRI 63-441 in the PAF and endotoxin models of hypotension in the rat and dog

Immunopharmacology
D A HandleyR N Saunders

Abstract

Intravenous administration of platelet-activating factor (PAF) produces dose-dependent hypotension in several species. We have evaluated a recently developed PAF antagonist, SRI 63-441, for its ability to inhibit the hypotensive effect of PAF in the rat and dog. In the rat, 100 ng/kg PAF produced a 38.6 +/- 5.1% decrease in carotid mean arterial pressure (MAP), followed by a 3.2 +/- 0.7 min recovery period for MAP to return to baseline values. SRI 63-441 reduced the hypotension response in the rat, where the ED50 values for inhibition of MAP were 0.16 mg/kg i.v. and 0.19 mg/kg i.v. for the recovery period. Dogs challenged with 1.5 micrograms/kg PAF i.v. demonstrated a 52 +/- 8% decrease in MAP that persisted for at least 15 min. The ED50 for inhibition of MAP by SRI 63-441 was 0.20 mg/kg i.v. Following injection of tritium-labeled SRI 63-441, 56.8 +/- 2.4% of the dose was recovered in the urine and 43.2 +/- 8.9% in the feces in the rats while in dogs 38.7 +/- 5.6% and 60.9 +/- 23.5% of the dose was excreted in the urine and feces, respectively. In the rat model of endotoxin-induced hypotension, SRI 63-441 given 1 min after a 5 mg/kg endotoxin challenge (which produced a 52 +/- 7% decrease in MAP), reversed the systemic effects,...Continue Reading

References

Jun 28, 1979·Nature·M ChignardJ Benveniste
Oct 29, 1979·Biochemical and Biophysical Research Communications·M L BlankE E Muirhead
Jan 1, 1986·International Archives of Allergy and Applied Immunology·R PattersonW J Houlihan
Feb 1, 1985·Immunopharmacology·P IñarreaM Sánchez-Crespo
Feb 26, 1985·European Journal of Pharmacology·Z TerashitaS Sumida
Apr 25, 1983·Life Sciences·Z TerashitaK Nishikawa
Oct 15, 1984·European Journal of Pharmacology·P IñarreaM S Crespo
Jan 21, 1983·European Journal of Pharmacology·P BessinJ Benveniste

Citations

Dec 1, 1991·Lipids·R RabinoviciG Feuerstein
Aug 20, 1991·Biochimica Et Biophysica Acta·J Lamotte-BrasseurJ J Godfroid
Sep 23, 1987·European Journal of Pharmacology·D A HandleyR N Saunders
Jan 1, 1988·Molecular Aspects of Medicine·N C OlsonC E McCall
Jan 1, 1991·Annals of the New York Academy of Sciences·R D Krell, M McCarthy
Jul 15, 1988·Biochemical and Biophysical Research Communications·R M Rubin, J T Rosenbaum

Related Concepts

Sandoz 63-441
Metazoa
Diastolic Blood Pressure
Canis familiaris
Endotoxins
Feces
Platelet Activating Factor
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Rats, Laboratory

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