PAROXETINE IS A NOVEL NITRIC-OXIDE SYNTHASE INHIBITOR

The selective serotonin reuptake inhibitor, paroxetine, has been repor ted to inhibit cytochrome P450 activity, Nitric oxide synthase (NOS) i s structurally homologous to cytochrome P450, Accordingly, in our stud y, we observed the effects of paroxetine on NOS activity, Seventeen is chemic heart disease (IHD) patients received paroxetine and fourteen r eceived nortriptyline for treatment of clinical depression defined by a score of 17 or higher on the Hamilton Rating Scale for Depression (H AM-D), Serum nitrite and nitrate levels were significantly decreased f ollowing paroxetine treatment but not nortriptyline treatment, Paroxet ine was also a more potent inhibitor of NOS enzyme activity than nortr iptyline, as measured by the conversion of [C-14] arginine to [C-14] c itrulline by hamster brain cytosols, In addition, paroxetine reversed the force-frequency relationship in isolated hamster papillary muscles in a manner analogous to that of known NOS inhibitors. Thus, paroxeti ne appears to be a novel NOS inhibitor in vitro and in vivo.