Pravadoline

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Pravadoline
File:Pravadoline.svg
Legal status
Legal status
  • In general: legal
Identifiers
CAS Number
PubChem CID
E number{{#property:P628}}
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Chemical and physical data
FormulaC23H26N2O3
Molar mass378.46 g/mol

Pravadoline (WIN 48098) is an antiinflammatory and analgesic drug, related in structure to 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.

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,[1] and it was eventually discovered that pravadoline represented the first compound from a novel class of cannabinoid agonists, the aminoalkylindoles.[2]

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),[3] 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.[4][5]



References

  1. Haubrich DR, Ward SJ, Baizman E, Bell MR, Bradford J, Ferrari R, Miller M, Perrone M, Pierson AK, Saelens JK, et al. Pharmacology of pravadoline: a new analgesic agent. Journal of Pharmacology and Experimental Therapeutics. 1990 Nov;255(2):511-22.
  2. Bell MR, D'Ambra TE, Kumar V, Eissenstat MA, Herrmann JL Jr, Wetzel JR, Rosi D, Philion RE, Daum SJ, Hlasta DJ, et al. Antinociceptive (aminoalkyl)indoles. Journal of Medicinal Chemistry. 1991 Mar;34(3):1099-1110.
  3. Everett RM, Descotes G, Rollin M, Greener Y, Bradford JC, Benziger DP, Ward SJ. Nephrotoxicity of pravadoline maleate (WIN 48098-6) in dogs: evidence of maleic acid-induced acute tubular necrosis. Fundamental and Applied Toxicology. 1993 Jul;21(1):59-65.
  4. D'Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beglin NC, et al. Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor. Journal of Medicinal Chemistry. 1992 Jan;35(1):124-35.
  5. Compton DR, Gold LH, Ward SJ, Balster RL, Martin BR. Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. Journal of Pharmacology and Experimental Therapeutics. 1992 Dec;263(3):1118-26.



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