polyunsaturated alkamides


Summary: Amides composed of unsaturated aliphatic FATTY ACIDS linked with AMINES by an amide bond. They are most prominent in ASTERACEAE; PIPERACEAE; and RUTACEAE; and also found in ARISTOLOCHIACEAE; BRASSICACEAE; CONVOLVULACEAE; EUPHORBIACEAE; MENISPERMACEAE; POACEAE; and SOLANACEAE. They are recognized by their pungent taste and for causing numbing and salivation.

Top Publications

  1. Forner Piquer I, Maradonna F, Gioacchini G, Santangeli S, Allarà M, Piscitelli F, et al. Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish. Endocrinology. 2017;158:3462-3476 pubmed publisher
    ..These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. ..
  2. Dauvois S, White R, Parker M. The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci. 1993;106 ( Pt 4):1377-88 pubmed
    ..Thus although ligand binding is not required by the estrogen receptor to undergo nucleocytoplasmic shuttling, this process can be disrupted by the binding of a pure antiestrogen. ..
  3. Martin G, Huang H, McIntosh A, Kier A, Schroeder F. Endocannabinoid Interaction with Human FABP1: Impact of the T94A Variant. Biochemistry. 2017;56:5147-5159 pubmed publisher
    ..Importantly, NAFLD has been associated with elevated hepatic levels of ECs and FABP1. ..
  4. Ahmad A, Daneva Z, Li G, Dempsey S, Li N, Poklis J, et al. Stimulation of diuresis and natriuresis by renomedullary infusion of a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase. Am J Physiol Renal Physiol. 2017;313:F1068-F1076 pubmed publisher
  5. Green B. Rapid recovery from capsaicin desensitization during recurrent stimulation. Pain. 1996;68:245-53 pubmed
    ..The implications these findings may have for hypotheses about the mechanisms of capsaicin desensitization and sensitization as well as for clinical applications of capsaicin as a topical analgesic are discussed. ..
  6. Stevens D, Lawless H. Putting out the fire: effects of tastants on oral chemical irritation. Percept Psychophys. 1986;39:346-50 pubmed
  7. Lawless H, Stevens D. Effects of oral chemical irritation on taste. Physiol Behav. 1984;32:995-8 pubmed
    ..The effects of piperine were more broad, with significant decrements in perceived intensity relative to emulsion controls for all substances. ..
  8. Rentmeister Bryant H, Green B. Perceived irritation during ingestion of capsaicin or piperine: comparison of trigeminal and non-trigeminal areas. Chem Senses. 1997;22:257-66 pubmed
  9. Maia J, Almada M, Silva A, Correia da Silva G, Teixeira N, Sá S, et al. The endocannabinoid system expression in the female reproductive tract is modulated by estrogen. J Steroid Biochem Mol Biol. 2017;174:40-47 pubmed publisher
    ..Thus, estradiol may have a direct regulatory role in the modulation of ECS in female reproductive tissues. ..

More Information


  1. Dessirier J, Nguyen N, Sieffermann J, Carstens E, O Mahony M. Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects. Chem Senses. 1999;24:405-13 pubmed
    ..This asymmetrical cross-desensitization pattern is similar to that observed between capsaicin and nicotine and constitutes an additional similarity between piperine and capsaicin. ..
  2. Thenmozhi K, Yoo Y. Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems. Drug Dev Ind Pharm. 2017;43:1501-1509 pubmed publisher
    ..Results suggest that the piperine solid dispersions prepared with improved in vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement. ..
  3. Uhl R, Roberts T, Papaliodis D, Mulligan M, Dubin A. Management of chronic musculoskeletal pain. J Am Acad Orthop Surg. 2014;22:101-10 pubmed publisher
    ..However, drug efficacy varies significantly by indication. Orthopaedic surgeons should be familiar with the widely available safe and effective nonnarcotic options for chronic musculoskeletal pain. ..
  4. Taketo M, Matsuda H. Short-term inhibition of GABAergic IPSCs induced by association of pre- and postsynaptic activation in the neonatal hippocampus. Neuropharmacology. 2017;121:39-48 pubmed publisher
    ..This inhibition is mediated by a mechanism involving mGluRs, mAChRs, and CB1 receptors, and potentiated by NMDA receptor activation. ..
  5. Lawless H, Stevens D. Responses by humans to oral chemical irritants as a function of locus of stimulation. Percept Psychophys. 1988;43:72-8 pubmed
  6. Di Scala C, Mazzarino M, Yahi N, Varini K, Garmy N, Fantini J, et al. Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells. Chem Phys Lipids. 2017;205:11-17 pubmed publisher
    ..Taken together, these data suggested that ceramide binds to AEA, increases its half-life and potentiates its cytotoxicity. Overall, these mechanisms account for a functional cross-talk between AEA and ceramide apoptotic pathways. ..
  7. Ma Z, Yuan Y, Zhang X, Xu S, Wang S, Tang Q. Piperine Attenuates Pathological Cardiac Fibrosis Via PPAR-?/AKT Pathways. EBioMedicine. 2017;18:179-187 pubmed publisher
    ..In conclusion, piperine attenuated cardiac fibrosis via the activation of PPAR-? and the resultant inhibition of AKT/GSK3?. ..
  8. Liu L, Simon S. Similarities and differences in the currents activated by capsaicin, piperine, and zingerone in rat trigeminal ganglion cells. J Neurophysiol. 1996;76:1858-69 pubmed
    ..Their different physiological responses evoked by these compounds can be rationalized, in part, by their very different activation and desensitization kinetics, and perhaps by the existence of different subtypes of vanilloid receptors. ..
  9. Lykkesfeldt A, Madsen M, Briand P. Altered expression of estrogen-regulated genes in a tamoxifen-resistant and ICI 164,384 and ICI 182,780 sensitive human breast cancer cell line, MCF-7/TAMR-1. Cancer Res. 1994;54:1587-95 pubmed
    ..Our results indicate that treatment with pure antiestrogens may be effective when patients become refractory to tamoxifen therapy. ..
  10. Berry M, Metzger D, Chambon P. Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J. 1990;9:2811-8 pubmed
    ..We also confirm that the wild type human oestrogen receptor has no ligand independent transcriptional activity. The implications of our results for the variable antagonist/agonist activity of anti-oestrogens in vivo are discussed. ..
  11. Panahi Y, Khalili N, Sahebi E, Namazi S, Reiner Z, Majeed M, et al. Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial. Complement Ther Med. 2017;33:1-5 pubmed publisher
    ..Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D. ..
  12. Stella N, Schweitzer P, Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature. 1997;388:773-8 pubmed
    ..Our results indicate that 2-AG is a second endogenous cannabinoid ligand in the central nervous system. ..
  13. Karlsson J, Gouveia Figueira S, Alhouayek M, Fowler C. Effects of tumour necrosis factor ? upon the metabolism of the endocannabinoid anandamide in prostate cancer cells. PLoS ONE. 2017;12:e0185011 pubmed publisher
    ..Further studies are necessary to determine the extent to which inflammatory mediators are involved in the abnormal endocannabinoid signalling system in prostate cancer. ..
  14. Murtaza G, Mermer P, Goldenberg A, Pfeil U, Paddenberg R, Weissmann N, et al. TASK-1 potassium channel is not critically involved in mediating hypoxic pulmonary vasoconstriction of murine intra-pulmonary arteries. PLoS ONE. 2017;12:e0174071 pubmed publisher
    ..While there is compelling evidence that TASK-1 is involved in the pathogenesis of pulmonary arterial hypertension in humans, the mouse does not appear to serve as a suitable model to study the underlying molecular mechanisms. ..
  15. Verma A, Kushwaha H, Srivastava A, Srivastava S, Jamal N, Srivastava K, et al. Piperine attenuates UV-R induced cell damage in human keratinocytes via NF-kB, Bax/Bcl-2 pathway: An application for photoprotection. J Photochem Photobiol B. 2017;172:139-148 pubmed publisher
    ..Therefore, we suggest the applicability of photostable PIP as photoprotective agent for human use. ..
  16. Gastón R, María Eugenia P, Das U, Eynard A. Polyunsaturated Fatty Acids Differentially Modulate Cell Proliferation and Endocannabinoid System in Two Human Cancer Lines. Arch Med Res. 2017;48:46-54 pubmed publisher
    ..The growth of tumor cells can be differentially modulated by fatty acids and, at least in part, can be attributed to their ability to act on the components of the endocannabinoid system. ..
  17. Datta A, Kim H, Lal M, McGee L, Johnson A, Moustafa A, et al. Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells. Cancer Lett. 2017;408:73-81 pubmed publisher
    ..Our findings suggest that MA is a potential drug candidate to suppress exosome biogenesis and secretion by CRPC cells. ..
  18. Zoerner A, Stichtenoth D, Engeli S, Batkai S, Winkler C, Schaumann F, et al. Allergen challenge increases anandamide in bronchoalveolar fluid of patients with allergic asthma. Clin Pharmacol Ther. 2011;90:388-91 pubmed publisher