4-Caffeoyl-1,5-quinide in roasted coffee inhibits [3H]naloxone binding and reverses anti-nociceptive effects of morphine in mice
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- de Paulis, T., Commers, P., Farah, A. et al. Psychopharmacology (2004) 176: 146. doi:10.1007/s00213-004-1876-9
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.
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.
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°C.
Extract of decaffeinated instant coffee produced a displacement Ki of 42±16 mg/l, while the Ki of a synthetic sample of 4-CQL was 4.4±0.4 μM. 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.
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.