Biomaterial Database

Paroxetine is a novel nitric oxide synthase inhibitor. 1996

M S Finkel, and F Laghrissi-Thode, and B G Pollock, and J Rong

Department of Medicine (Cardiology), University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, PA, USA.

The selective serotonin reuptake inhibitor, paroxetine, has been reported to inhibit cytochrome P450 activity. Nitric oxide synthase (NOS) is structurally homologous to cytochrome P450. Accordingly, in our study, we observed the effects of paroxetine on NOS activity. Seventeen ischemic heart disease (IHD) patients received paroxetine and fourteen received nortriptyline for treatment of clinical depression defined by a score of 17 or higher on the Hamilton Rating Scale for Depression (HAM-D). Serum nitrite and nitrate levels were significantly decreased following paroxetine treatment but not nortriptyline treatment. Paroxetine was also a more potent inhibitor of NOS enzyme activity than nortriptyline, as measured by the conversion of [14C] arginine to [14C] citrulline 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, paroxetine appears to be a novel NOS inhibitor in vitro and in vivo.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010210	Papillary Muscles	Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae.	Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012701	Serotonin	A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D017374	Paroxetine	A serotonin uptake inhibitor that is effective in the treatment of depression.	Aropax,BRL-29060,FG-7051,Paroxetine Acetate,Paroxetine Hydrochloride,Paroxetine Hydrochloride Anhydrous,Paroxetine Hydrochloride Hemihydrate,Paroxetine Hydrochloride, Hemihydrate,Paroxetine Maleate,Paroxetine, cis-(+)-Isomer,Paroxetine, cis-(-)-Isomer,Paroxetine, trans-(+)-Isomer,Paxil,Seroxat,BRL 29060,BRL29060,FG 7051,FG7051
D019001	Nitric Oxide Synthase	An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.	NO Synthase,Nitric-Oxide Synthase,Nitric-Oxide Synthetase,Nitric Oxide Synthetase,Oxide Synthase, Nitric,Synthase, Nitric Oxide