Abstract
Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin.
Keywords:
Gastric-sparing NSAIDs; NO-NSAIDs; NO-aspirin; NO-naproxen; Nitric oxide donors.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents, Non-Steroidal / chemistry
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
-
Anti-Inflammatory Agents, Non-Steroidal / toxicity
-
Area Under Curve
-
Aspirin / analogs & derivatives*
-
Aspirin / chemistry
-
Aspirin / pharmacokinetics
-
Aspirin / pharmacology
-
Aspirin / toxicity
-
Blood Platelets / drug effects
-
Blood Platelets / enzymology
-
Cyclooxygenase 1 / chemistry
-
Cyclooxygenase 1 / metabolism
-
Cyclooxygenase 2 / chemistry
-
Cyclooxygenase 2 / metabolism
-
Drug Design
-
Drug Stability
-
Gastric Mucosa / drug effects
-
Half-Life
-
Humans
-
Naproxen / analogs & derivatives*
-
Naproxen / chemistry
-
Naproxen / pharmacokinetics
-
Naproxen / pharmacology
-
Naproxen / toxicity
-
Nitrates / chemistry*
-
Nitrates / pharmacokinetics
-
Nitrates / pharmacology
-
Nitrates / toxicity
-
Nitric Oxide / metabolism
-
Platelet Aggregation Inhibitors / chemistry
-
Platelet Aggregation Inhibitors / pharmacokinetics
-
Platelet Aggregation Inhibitors / pharmacology
-
Platelet Aggregation Inhibitors / toxicity
-
Prodrugs / chemistry*
-
Prodrugs / pharmacokinetics
-
Prodrugs / pharmacology
-
Prodrugs / toxicity
-
ROC Curve
-
Rats
-
Rats, Sprague-Dawley
-
Thromboxane B2 / metabolism
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
N-acetyl-S-(alpha-methyl-4-(2-methylpropyl)benzeneacetyl)cysteine 4-(nitrooxy)butyl ester
-
Nitrates
-
Platelet Aggregation Inhibitors
-
Prodrugs
-
naproxen-n-butyl nitrate
-
Nitric Oxide
-
Thromboxane B2
-
Naproxen
-
Cyclooxygenase 1
-
Cyclooxygenase 2
-
Aspirin