Chlorpromazine inhibits both the constitutive nitric oxide synthase and the induction of nitric oxide synthase after LPS challenge.
The effects of chlorpromazine on either the activity of mouse brain nitric oxide synthase or the induction of lung nitric oxide synthase in mice and rats were studied. Chlorpromazine inhibited the nitric oxide synthase activity in mouse brain cytosol. This effect could be reversed by adding an excess of calmodulin. In addition, chlorpromazine was able to inhibit the induction of lung nitric oxide synthase, in both species, after LPS administration. Furthermore, chlorpromazine also inhibited arginase activity in mouse lung cytosol.
Palacios
M
M
Pharmacology and Toxicology Dept., Center of Pharmaceutical Chemistry, Havana, Cuba.
Padron
J
J
Glaria
L
L
Rojas
A
A
Delgado
R
R
Knowles
R
R
Moncada
S
S
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D001921:Brain / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology*; D002956:Citrulline / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000209:etiology
D008070:Lipopolysaccharides; D002956:Citrulline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase; D002746:Chlorpromazine