No side effect painkillers
doi:10.1038/nindia.2009.292 Published online 17 September 2009
Researchers have designed a new class of pro-drugs of non-steroidal anti-inflammatory drugs (NSAIDs) that can reduce toxic effects on gastric cells thereby reducing pain.
Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) drugs aspirin and diclofenac induce severe gastrointestinal toxicity leading to bleeding, ulceration and perforation. To overcome this, the researchers synthesised nitric oxide (NO) releasing pro-drugs NO-Aspirin and NO-Diclofenac using with a new technology called disulfide linker technology.
NO is known to mediate gastrointestinal mucosa defense suppressing NSAID-induced side effects. The pro-drugs broke down to generate nitrate ions and released free drugs. Nitrate ion is further converted to nitrite ion by oral bacterial reductase, an enzyme. This nitrite ion is reduced to NO via nitrous acid in the acidic environment of the stomach.
"While both the parent drugs caused significant gastric damage, NO-NSAIDs did not cause any gastrointestinal damage," says lead researcher Apparao Satyam. The gastric-sparing effect is due to the beneficial actions of NO released from the NO-NSAIDs, he adds.
- Nemmani, V. S. K. et al. NO-NSAIDs: Gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs. Bioorg. Med. Chem. Lett. 19, 5297-5301(2009)