Abstract
Rationale
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.
Objectives
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°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 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.
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.
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References
Ahlijanian MK, Takemori AE (1986) The effect of chronic administration of caffeine on morphine-induced analgesia, tolerance and dependency in mice. Eur J Pharmacol 120:25–32
Bennat C, Engelhardt UH, Kiehne A, Wirries FM, Maier HG (1994) HPLC analysis of chlorogenic acid lactones in roasted coffee. Lebensm Unters Forsch 199:17–21
Bolumar F, Olsen J, Rebogliato M, Bisanti L (1997) Caffeine intake and delayed conception: a European multicenter study on infertility and subfecundity. Am J Epidemiol 145:324–334
Boublik JH, Quinn MJ, Clements JA, Herington AC, Wynne KN, Funder JW (1983) Coffee contains potent opiate receptor binding activity. Nature 301:246–248
Celerier E, Simonnet G, Maqldonado R (2004) Prevention of fentanyl-induced delayed pronociceptive effects in mice lacking the protein kinase C-gamma gene. Neuropharmacology 46:264–272
Clifford MN (1985) Chlorogenic acids. In: Clarke RJ, Macrae R (eds) Coffee (vol 1: chemistry). Elsevier, London, pp 153–202
Clifford MN (2000) Chlorogenic acids and other cinnamates—nature, occurrence, dietary burden, absorption and metabolism. J Sci Food Agric 80:1033–1043
Crain SM, Shen K-F (2001) Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low dose of naltrexone, unmasking potent opioid analgesia. Brain Res 888:75–82
de Paulis T, Martin PR (2004) Effects of non-caffeine constituents in roasted coffee on the brain. In: Nehlig A (ed) Coffee, tea, chocolate and the brain. CRC, Boca Raton, Fla., pp 185–195
de Paulis T, Schmidt DE, Bruchey AK, Kirby MT, McDonald MP, Commers P, Lovinger DM, Martin PR (2002) Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter. Eur J Pharmacol 442:215–223
Elmer GI, Pieper JO, Negus SS, Woods JH (1998) Genetic variance in nociception and its relationship to the potency of morphine-induced analgesia in thermal and chemical tests. Pain 75:129–140
Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133
Granados-Soto V, Castaneda-Hernandez G (1999) A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effects of nonsteroidal anti-inflammatory drugs by caffeine. J Pharmacol Toxicol 42:67–72
Huynh-Ba T (1995) Preparation of quinic acid derivatives. US Patent 5,401,858
James JE (1998) Acute and chronic effects of caffeine on performance, mood, headache, and sleep. Neuropsychobiology 38:32–41
King CD, Devine DP, Vierck CJ, Rodgers J, Yezierski RP (2003) Differential effects of stress on escape and reflex responses to nociceptive thermal stimuli in the rat. Brain Res 987:214–222
Larcher A, Laulin JP, Celerier, Le Moal M, Simonnet G (1998) Acute tolerance associated with a single opiate administration: involvement of N-methyl-d-aspartate-dependent pain facilitation systems. Neuroscience 84:583–589
Lattanzi R, Negri L, Schmidhammer H, Giannini E (2002) Antinociceptive activity of a novel buprenorphine analogue. Life Sci 70:2177–2185
Mauderli AP, Acosta-Rua A, Vierck CJ (2000) An operant assay of thermal pain in conscious, unrestrained rats. J Neurosci Meth 97:19–29
McGilliard KL, Takemori AE (1978) Antagonism by naloxone of narcotic-induced respiratory depression and analgesia. J Pharmacol Exp Ther 207:494–503
McPartland JM, Mitchell JA (1997) Caffeine and chronic back pain. Arch Phys Med Rehabil 78:61–63
Mogil JS, Kest B, Sadowski B, Belknap JK (1996) Differential genetic mediation of sensitivity to morphine in genetic models of opiate antinociception: influence of nociceptive assay. J Pharmacol Exp Ther 276:532–544
Pert CB, Snyder SH (1974) Opiate receptor binding of agonists and antagonists affected differentially by sodium. Mol Pharmacol 10:868–879
Plone MA, Emerich DF, Lindner MD (1996) Individual differences in the hot plate test and effects of habituation on sensitivity to morphine. Pain 66:265–270
Schilter B, Cavin C, Tritcher A, Constable A (2001) Health effects and safety considerations. In: Clarke RJ, Vitzthum OG (eds) Coffee. Recent developments. Blackwell, Cornwall, pp 165–183
Schrader K, Kiehne A, Engelhardt UH, Maier HG (1996) Determination of chlorogenic acids with lactones in roasted coffee. J Sci Food Agric 71:392–398
Strubelt O, Kaschube M, Zetler G (1986) Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo. Experientia 42:35–37
Sung K-W, Kirby M, McDonald MP, Lovinger DM, Delpire E (2000) Abnormal GABAA receptor-mediated currents in dorsal root ganglion neurons isolated from Na–K–2Cl cotransporter null mice. J Neurosci 20:7531–7538
Trugo LC, Macrae R (1984a) Chlorogenic acid composition of instant coffee. Analyst 109:263–266
Trugo LC, Macrae R (1984b) A study of the effect of roasting on the chlorogenic acid composition in coffee using HPLC. J Sci Food Agric 15:219–227
Ugert R, Katan MB (1997) The cholesterol-raising factor from coffee beans. Annu Rev Nutr 17:305–324
Wynne K, Boublik JH, Drummer OH, Rae ID, Funder JW (1985) Opiate antagonists. WIPO Patent 8,601,508
Wynne KN, Familari M, Boublik JH, Drummer OH, Rae ID, Funder JW (1987) Isolation of opiate receptor ligands in coffee. Clin Exp Pharmacol Physiol 14:785–790
Acknowledgements
This study was funded by the Vanderbilt Institute for Coffee Studies, which is supported by funds from national coffee federations of Brazil, Colombia, Guatemala, Mexico, and Japan. Support from National Coffee Association of USA and grants from Kraft, Nestle, Sara Lee, and Starbuck companies are gratefully acknowledged.
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de Paulis, T., Commers, P., Farah, A. et al. 4-Caffeoyl-1,5-quinide in roasted coffee inhibits [3H]naloxone binding and reverses anti-nociceptive effects of morphine in mice. Psychopharmacology 176, 146–153 (2004). https://doi.org/10.1007/s00213-004-1876-9
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DOI: https://doi.org/10.1007/s00213-004-1876-9