title: 4-Caffeoyl-1,5-quinide in roasted coffee inhibits [3H]naloxone binding and reverses anti-nociceptive effects of morphine in mice.
abstract: BACKGROUND
  Cinnamoylquinides are formed from the corresponding chlorogenic acids during coffee roasting. Instant coffee has been shown to displace binding of the mu opioid receptor antagonist, [3H]naloxone, but the putative active agent, feruloylquinide, has not been characterized.
  
  
  OBJECTIVE
  The goal was to identify the active agent(s) in coffee by measuring the binding affinity of individual cinnamoyl-1,5-quinides to the human mu opioid receptor, and determine the effects of these compounds on morphine-induced anti-nociceptive behavior in mice.
  
  
  METHODS
  Cinnamoyl-1,5-quinides in extracts of decaffeinated instant coffee were quantified by reverse-phase HPLC comparisons with synthetic samples of 3-coumaroyl-1,5-quinide and 4-coumaroyl-1,5-quinide, 3-caffeoyl-1,5-quinide and 4-caffeoyl-1,5-quinide (4-CQL) 3-feruloyl-1,5-quinide and 4-feruloyl-1,5-quinides and 3,4-dicaffeoyl-1,5-quinide (DICAQ). Affinities of the cinnamoyl-1,5-quinides and decaffeinated instant coffee extract were determined by displacement of [3H]naloxone binding in cultured HEK-MOR cells. Inhibition of the anti-nociceptive activity of morphine (1 mg/kg IP) was determined in C57BL/6J mice using the hot plate test at 52 degrees C.
  
  
  RESULTS
  Extract of decaffeinated instant coffee produced a displacement K(i) of 42+/-16 mg/l, while the K(i) of a synthetic sample of 4-CQL was 4.4+/-0.4 microM. Compounds with a cinnamoyl substituent in the 4-position of the quinide, i.e. 4-CQL, DICAQ, 3,4-diferuloyl-1,5-quinide, and 3,4-dicoumaroyl-1,5-quinide, had affinities for the mu opioid receptor in the low micromolar range. In the hot plate test, coffee extract, containing 0.78% of 4-CQL, reversed the anti-nociceptive effect of morphine at 10 mg/kg IP. Two cinnamoyl-1,5-quinides found in roasted coffee, DICAQ, and 4-CQL, were active at 1 and 0.1 mg/kg IP, respectively.
  
  
  CONCLUSIONS
  These results suggest that the previously reported anti-opioid activity of instant coffee is caused primarily by the presence of 4-CQL, and to lesser extent by other cinnamoyl-1,5-quinides.
authors.affiliation: Department of Psychiatry, Vanderbilt Institute for Coffee Studies, Vanderbilt University School of Medicine, MCN AA-2213, Nashville, TN 37232, USA. tomas.depaulis@vanderbilt.edu
authors.forename: Tomas
authors.initials: T
authors.lastname: de Paulis
authors.forename: Patricia
authors.initials: P
authors.lastname: Commers
authors.forename: Adriana
authors.initials: A
authors.lastname: Farah
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhao
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDonald
authors.forename: Ruggero
authors.initials: R
authors.lastname: Galici
authors.forename: Peter R
authors.initials: PR
authors.lastname: Martin
mesh_terms: D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D003069:Coffee; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D003069:Coffee; D017450:Receptors, Opioid, mu; C472707:caffeoylquinic acid; D011801:Quinic Acid; D014316:Tritium; D009270:Naloxone; D009020:Morphine