Pravadoline is a nonacidic, aminoalkylindole analgesic agent that inhibits cyclooxygenase.pravadoline sales,WIN 48098,am964,rcs 4 cannabinoid,win55 512 2
Like NSAIDs, pravadoline inhibits prostaglandin synthesis (IC50 = 5 μM in mouse brain microsomes) and displays antinociceptive activity (ED50 = 26 mg/kg in an acetylcholine-
In contrast to NSAIDs, pravadoline inhibits neuronally stimulated contractions in mouse vas deferens preparations (IC50 = 0.45 μM), an effect similar to that which is produced by opioid analgesics, yet is not attenuated by the opioid receptor antagonist, naloxone.
Pravadoline does not produce gastrointestinal irritation following acute or chronic administration to rodents.
Pravadoline (WIN 48,098) is an antiinflammatory and analgesic drug with an IC50 of 4.9 μM and a Ki of 2511 nM at CB1, related in structure to nonsteroidal anti-inflammatory drugs (NSAIDs) such as indometacin. It was developed in the 1980s as a new antiinflammatory and prostaglandin synthesis inhibitor, acting through inhibition of the enzyme cyclooxygenase (COX).pravadoline sales,WIN 48098,am964,rcs 4 cannabinoid,win55 512 2
However, pravadoline was found to exhibit unexpectedly strong analgesic effects, which appeared at doses ten times smaller than the effective anti-inflammatory dose and so could not be explained by its action as a COX inhibitor.
These effects were not blocked by opioid antagonists such as naloxone, and it was eventually discovered that pravadoline represented the first compound from a novel class of cannabinoid agonists, the aminoalkylindoles.
Pravadoline was never developed for use as an analgesic, partly due to toxicity concerns (although these were later shown to be a result of the salt form that the drug had been prepared in rather than from the pravadoline itself),
however the discovery of cannabinoid activity in this structurally novel family of drugs led to the discovery of several new cannabinoid agonists, including the drug WIN 55,212-2, which is now widely used in scientific research.
Chemical and physical data
Molar mass 378.46 g/mol