1999 - SK&F 106615 (atiprimod).
1: Toxicol Appl Pharmacol. 1999 Aug 15;159(1):9-17. Related Articles, Links
Selective inhibition of phospholipases by atiprimod, a macrophage targeting antiarthritic compound.
Handler JA, Badger A, Genell CA, Klinkner AM, Kassis S, Waites CR, Bugelski PJ.
Department of Toxicology, SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania, 19426, USA.
Azaspiranes are cationic amphiphilic compounds that are active in a number of models of autoimmune disease and transplantation.
Repeated administration of cationic amphiphiles induces phospholipid accumulation in a variety of species.
The present study was conducted to explore the mechanism of phospholipid accumulation in rats caused by treatment with the novel azaspirane, SK&F 106615 (atiprimod).
Atiprimod inhibited the activities of partially purified phospholipases A(2) and C, but not D, in a noncompetitive manner in vitro.
Treatment of rats for 28 days with 10 mg/kg/day of atiprimod increased the contents of arachidonate-containing molecular species within plasmalogen subclasses of hepatic phosphatidylcholine and phosphatidylethanolamine.
In contrast, diacyl-linked species were not affected, indicating a selective effect upon an hepatic plasmalogen-selective phospholipase A(2).
Taken together, the data suggest that the beneficial effects of atiprimod in autoimmune diseases may involve inhibition of phospholipase A(2) and C activities.
Further, the data suggest that atiprimod is a selective inhibitor of plasmalogen-selective phospholipase A(2) in vivo. Copyright 1999 Academic Press.
PMID: 10448120 [PubMed - indexed for MEDLINE]
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