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The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation

Yıl 2014, Cilt: 2014 Sayı: 2, 115 - 120, 07.08.2014

Ahmet Ulugöl

https://doi.org/10.5152/balkanmedj.2014.13103

Öz

Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms. Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the enzymes playing a role in endocannabinoid metabolism. Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme. In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions. (Balkan Med J 2014;31:115-20).

Anahtar Kelimeler

2-AG anandamide endocannabinoids FAAH MAGL pain

Kaynakça

  • Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol 2001;63:569-611. [CrossRef]
  • Walker JM, Huang SM. Cannabinoid analgesia. Pharmacol Ther 2002;95:127-35. [CrossRef]
  • Di Marzo V. Targeting the endocannabinoid system: to enhance or re- duce? Nat Rev Drug Discov 2008;7:438-55. [CrossRef]
  • Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Disord Drug Targets 2009;8:403-21. [CrossRef]
  • Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibili- ties. Philos Trans R Soc Lond B Biol Sci 2012;367:3353-63. [CrossRef]
  • Ulugol A, Ozyigit F, Yesilyurt O, Dogrul A. The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketoro- lac. Anesth Analg 2006;102:443-7. [CrossRef]
  • Gunduz O, Karadag HC, Ulugol A. Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice. Pharmacol Biochem Behav 2011;99:540-4. [CrossRef]
  • Dogrul A, Gul H, YildIz O, Bilgin F, Guzeldemir ME. Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its anti- nociceptive effect. Neurosci Lett 2004;368:82-6. [CrossRef]
  • Ulugol A, Karadag HC, Ipci Y, Tamer M, Dokmeci I. The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. Neurosci Lett 2004;371:167-70. [CrossRef]
  • Munro S, Thomas KL, Abushaar M. Molecular Characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61-5. [CrossRef]
  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Struc- ture of a cannabinoid receptor and functional expression of the cloned Cdna. Nature 1990;346:561-4. [CrossRef]
  • Dogrul A, Seyrek M, Yalcin B, Ulugol A. Involvement of descending se- rotonergic and noradrenergic pathways in CB1 receptor-mediated anti- nociception. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:97- 105. [CrossRef]
  • Dogrul A, Seyrek M, Yalcin B, Ulugol A. Involvement of serotonergic system in cannabinoid analgesia. In: Van Bockstaele EJ, editor. Endo- cannabinoid regulation of monoamines in psychiatric and neurological disorders. New York: Springer; 2013:277-95. [CrossRef]
  • Guindon J, Beaulieu P, Hohmann AG. Pharmacology of the cannabinoid system. In: Beaulieu P, Lussier D, Porreca F, Dickenson AH, editors. Pharmacology of pain. Seattle: IASP Press; 2010:6.
  • Richardson JD. Cannabinoids modulate pain by multiple mechanisms of action. J Pain 2000;1:2-14. [CrossRef]
  • Manzanares J, Julian MD, Carrascosa A. Role of the cannabinoid sys- tem in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol 2006;4:239-57. [CrossRef]
  • Millan MJ. Descending control of pain. Prog Neurobiol 2002;66:355- 474. [CrossRef]
  • Meng ID, Manning BH, Martin WJ, Fields HL. An analgesia circuit ac- tivated by cannabinoids. Nature 1998;395:381-3. [CrossRef]
  • Dogrul A, Gul H, Akar A, YildIz O, Bilgin F, Guzeldemir E. Topical can- nabinoid antinociception: synergy with spinal sites. Pain 2003;105:11-6. [CrossRef]
  • Malan TP, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F. In- hibition of pain responses by activation of CB2 cannabinoid receptors. Chemistry and Physics of Lipids 2002;121:191-200. [CrossRef]
  • Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psy- chotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009;30:515-27. [CrossRef]
  • Starowicz K, Di Marzo V. Non-psychotropic analgesic drugs from the endocannabinoid system: “Magic bullet” or “multiple-target” strategies? Eur J Pharmacol 2013;716:41-53. [CrossRef]
  • Wright MJ, Vandewater SA, Taffe MA. Cannabidiol attenuates deficits of visuospatial associative memory induced by Delta 9tetrahydrocan- nabinol. Brit J Pharmacol 2013;170:1365-73. [CrossRef]
  • Sastre-Garriga J, Vila C, Clissold S, Montalban X. THC and CBD oromu- cosal spray (Sativex (R)) in the management of spasticity associated with multiple sclerosis. Expert Rev Neurother 2011;11:627-37. [CrossRef]
  • Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. Can Med Assoc J 2008;178:1669-78. [CrossRef]
  • Toth C, Mawani S, Brady S, Chan C, Liu CX, Mehina E, et al. An en- riched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. [CrossRef]
  • Zogopoulos P, Vasileiou I, Patsouris E, Theocharis SE. The role of endo- cannabinoids in pain modulation. Fund Clin Pharmacol 2013;27:64-80.
  • Cascio MG. PUFA-derived endocannabinoids: an overview. P Nutr Soc 2013;72:451-9. [CrossRef]
  • Di Marzo V. Endocannabinoids: synthesis and degradation. Rev Physiol Biochem Pharmacol 2008;160:1-24.
  • Fowler CJ. Anandamide uptake explained? Trends Pharmacol Sci 2012;33:181-5. [CrossRef]
  • Jhaveri MD, Richardson D, Chapman V. Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain. Brit J Pharmacol 2007;152:624-32. [CrossRef]
  • Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA 2003;290:1757-62. [CrossRef]
  • Pryce G, Visintin C, Ramagopalan SV, Al-Izki S, De Faveri LE, Nua- mah RA, et al. Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists. FASEB J 2014;28:117-30. [CrossRef]
  • Kalliomaki J, Annas P, Huizar K, Clarke C, Zettergren A, Karlsten R, et al. Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in hu- man capsaicin-induced pain and hyperalgesia. Clin Exp Pharmacol P 2013;40:212-8. [CrossRef]
  • Ostenfeld T, Price J, Albanese M, Bullman J, Guillard F, Meyer I, et al. A randomized, controlled study to investigate the analgesic efficacy of single doses of the cannabinoid receptor-2 agonist GW842166, ibupro- fen or placebo in patients with acute pain following third molar tooth extraction. Clin J Pain 2011;27:668-76. [CrossRef]
  • Atwood BK, Straiker A, Mackie K. CB2: therapeutic target-in-waiting. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:16-20. [CrossRef]
  • Smith PA, Selley DE, Sim-Selley LJ, Welch SP. Low dose combination of morphine and [Delta]9-tetrahydrocannabinol circumvents antinoci- ceptive tolerance and apparent desensitization of receptors. Eur J Phar- macol 2007;571:129-37. [CrossRef]
  • Pertwee RG. Elevating endocannabinoid levels: pharmacological strate- gies and potential therapeutic applications. Proc Nutr Soc 2014;73:96- 105. [CrossRef]
  • Maione S, Costa B, Di Marzo V. Endocannabinoids: a unique opportuni- ty to develop multitarget analgesics. Pain 2013;154:S87-93. [CrossRef]
  • Piscitelli F, Di Marzo V. “Redundancy” of Endocannabinoid Inactiva- tion: New Challenges and Opportunities for Pain Control. ACS Chem Neurosci 2012;3:356-63. [CrossRef]
  • Naidu PS, Kinsey SG, Guo TL, Cravatt BF, Lichtman AH. Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase. J Phar- macol Exp Ther 2010;334:182-90. [CrossRef]
  • Caprioli A, Coccurello R, Rapino C, Di Serio S, Di Tommaso M, Vertechy M, et al. The novel reversible fatty acid amide hydrolase in- hibitor ST4070 increases endocannabinoid brain levels and counteracts neuropathic pain in different animal models. J Pharmacol Exp Ther 2012;342:188-95. [CrossRef]
  • Huggins JP, Smart TS, Langman S, Taylor L, Young T. An efficient ran- domised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocan- nabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain 2012;153:1837-46. [CrossRef]
  • Fowler CJ, Naidu PS, Lichtman A, Onnis V. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1. Brit J Pharmacol 2009;156:412-9. [CrossRef]
  • Morera E, De Petrocellis L, Morera L, Moriello AS, Ligresti A, Nalli M, et al. Synthesis and biological evaluation of piperazinyl carba- mates and ureas as fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channel dual ligands. Bioorg Med Chem Lett 2009;19:6806-9. [CrossRef]
  • Costa B, Bettoni I, Petrosino S, Comelli F, Giagnoni G, Di Marzo V. The dual fatty acid amide hydrolase/TRPV1 blocker, N-arachidonoyl- serotonin, relieves carrageenan-induced inflammation and hyperalgesia in mice. Pharmacol Res 2010;61:537-46. [CrossRef]
  • Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG, et al. Chronic monoacylglycerol lipase blockade causes functional an- tagonism of the endocannabinoid system. Nat Neurosci 2010;13:1113- U111. [CrossRef]
  • Niphakis MJ, Johnson DS, Ballard TE, Stiff C, Cravatt BF. O-hydroxy- acetamide carbamates as a highly potent and selective class of endo- cannabinoid hydrolase inhibitors. ACS Chem Neurosci 2012;3:418-26. [CrossRef]
  • Fu J, Bottegoni G, Sasso O, Bertorelli R, Rocchia W, Masetti M, et al. A catalytically silent FAAH-1 variant drives anandamide transport in neurons. Nat Neurosci 2012;15:64-U82. [CrossRef]
  • Hogestatt ED, Jonsson BAG, Ermund A, Andersson DA, Bjork H, Alexander JP, et al. Conversion of acetaminophen to the bioactive N- acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. J Biol Chem 2005;280:31405-12. [CrossRef]
  • Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, et al. Endocannabinoid and serotonergic systems are needed for acetamin- ophen-induced analgesia. Pain 2008;139:190-200. [CrossRef]
  • Rogosch T, Sinning C, Podlewski A, Watzer B, Schlosburg J, Lichtman AH, et al. Novel bioactive metabolites of dipyrone (metamizol). Bioorg Med Chem 2012;20:101-7. [CrossRef]
  • Elmas P, Ulugol A. Involvement of cannabinoid CB1 receptors in the antinociceptive effect of dipyrone. J Neural Transm 2013;120:1533-8. [CrossRef]
  • Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A. The analgesic ac- tivity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. Eur J Pharmacol 2006;531:280-1. [CrossRef]
  • Escobar W, Ramirez K, Avila C, Limongi R, Vanegas H, Vazquez E. Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur J Pain 2012;16:676- 89. [CrossRef]

The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation

Yıl 2014, Cilt: 2014 Sayı: 2, 115 - 120, 07.08.2014

Ahmet Ulugöl

https://doi.org/10.5152/balkanmedj.2014.13103

Öz

Kaynakça

  • Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol 2001;63:569-611. [CrossRef]
  • Walker JM, Huang SM. Cannabinoid analgesia. Pharmacol Ther 2002;95:127-35. [CrossRef]
  • Di Marzo V. Targeting the endocannabinoid system: to enhance or re- duce? Nat Rev Drug Discov 2008;7:438-55. [CrossRef]
  • Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Disord Drug Targets 2009;8:403-21. [CrossRef]
  • Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibili- ties. Philos Trans R Soc Lond B Biol Sci 2012;367:3353-63. [CrossRef]
  • Ulugol A, Ozyigit F, Yesilyurt O, Dogrul A. The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketoro- lac. Anesth Analg 2006;102:443-7. [CrossRef]
  • Gunduz O, Karadag HC, Ulugol A. Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice. Pharmacol Biochem Behav 2011;99:540-4. [CrossRef]
  • Dogrul A, Gul H, YildIz O, Bilgin F, Guzeldemir ME. Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its anti- nociceptive effect. Neurosci Lett 2004;368:82-6. [CrossRef]
  • Ulugol A, Karadag HC, Ipci Y, Tamer M, Dokmeci I. The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. Neurosci Lett 2004;371:167-70. [CrossRef]
  • Munro S, Thomas KL, Abushaar M. Molecular Characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61-5. [CrossRef]
  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Struc- ture of a cannabinoid receptor and functional expression of the cloned Cdna. Nature 1990;346:561-4. [CrossRef]
  • Dogrul A, Seyrek M, Yalcin B, Ulugol A. Involvement of descending se- rotonergic and noradrenergic pathways in CB1 receptor-mediated anti- nociception. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:97- 105. [CrossRef]
  • Dogrul A, Seyrek M, Yalcin B, Ulugol A. Involvement of serotonergic system in cannabinoid analgesia. In: Van Bockstaele EJ, editor. Endo- cannabinoid regulation of monoamines in psychiatric and neurological disorders. New York: Springer; 2013:277-95. [CrossRef]
  • Guindon J, Beaulieu P, Hohmann AG. Pharmacology of the cannabinoid system. In: Beaulieu P, Lussier D, Porreca F, Dickenson AH, editors. Pharmacology of pain. Seattle: IASP Press; 2010:6.
  • Richardson JD. Cannabinoids modulate pain by multiple mechanisms of action. J Pain 2000;1:2-14. [CrossRef]
  • Manzanares J, Julian MD, Carrascosa A. Role of the cannabinoid sys- tem in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol 2006;4:239-57. [CrossRef]
  • Millan MJ. Descending control of pain. Prog Neurobiol 2002;66:355- 474. [CrossRef]
  • Meng ID, Manning BH, Martin WJ, Fields HL. An analgesia circuit ac- tivated by cannabinoids. Nature 1998;395:381-3. [CrossRef]
  • Dogrul A, Gul H, Akar A, YildIz O, Bilgin F, Guzeldemir E. Topical can- nabinoid antinociception: synergy with spinal sites. Pain 2003;105:11-6. [CrossRef]
  • Malan TP, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F. In- hibition of pain responses by activation of CB2 cannabinoid receptors. Chemistry and Physics of Lipids 2002;121:191-200. [CrossRef]
  • Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psy- chotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009;30:515-27. [CrossRef]
  • Starowicz K, Di Marzo V. Non-psychotropic analgesic drugs from the endocannabinoid system: “Magic bullet” or “multiple-target” strategies? Eur J Pharmacol 2013;716:41-53. [CrossRef]
  • Wright MJ, Vandewater SA, Taffe MA. Cannabidiol attenuates deficits of visuospatial associative memory induced by Delta 9tetrahydrocan- nabinol. Brit J Pharmacol 2013;170:1365-73. [CrossRef]
  • Sastre-Garriga J, Vila C, Clissold S, Montalban X. THC and CBD oromu- cosal spray (Sativex (R)) in the management of spasticity associated with multiple sclerosis. Expert Rev Neurother 2011;11:627-37. [CrossRef]
  • Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. Can Med Assoc J 2008;178:1669-78. [CrossRef]
  • Toth C, Mawani S, Brady S, Chan C, Liu CX, Mehina E, et al. An en- riched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. [CrossRef]
  • Zogopoulos P, Vasileiou I, Patsouris E, Theocharis SE. The role of endo- cannabinoids in pain modulation. Fund Clin Pharmacol 2013;27:64-80.
  • Cascio MG. PUFA-derived endocannabinoids: an overview. P Nutr Soc 2013;72:451-9. [CrossRef]
  • Di Marzo V. Endocannabinoids: synthesis and degradation. Rev Physiol Biochem Pharmacol 2008;160:1-24.
  • Fowler CJ. Anandamide uptake explained? Trends Pharmacol Sci 2012;33:181-5. [CrossRef]
  • Jhaveri MD, Richardson D, Chapman V. Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain. Brit J Pharmacol 2007;152:624-32. [CrossRef]
  • Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA 2003;290:1757-62. [CrossRef]
  • Pryce G, Visintin C, Ramagopalan SV, Al-Izki S, De Faveri LE, Nua- mah RA, et al. Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists. FASEB J 2014;28:117-30. [CrossRef]
  • Kalliomaki J, Annas P, Huizar K, Clarke C, Zettergren A, Karlsten R, et al. Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in hu- man capsaicin-induced pain and hyperalgesia. Clin Exp Pharmacol P 2013;40:212-8. [CrossRef]
  • Ostenfeld T, Price J, Albanese M, Bullman J, Guillard F, Meyer I, et al. A randomized, controlled study to investigate the analgesic efficacy of single doses of the cannabinoid receptor-2 agonist GW842166, ibupro- fen or placebo in patients with acute pain following third molar tooth extraction. Clin J Pain 2011;27:668-76. [CrossRef]
  • Atwood BK, Straiker A, Mackie K. CB2: therapeutic target-in-waiting. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:16-20. [CrossRef]
  • Smith PA, Selley DE, Sim-Selley LJ, Welch SP. Low dose combination of morphine and [Delta]9-tetrahydrocannabinol circumvents antinoci- ceptive tolerance and apparent desensitization of receptors. Eur J Phar- macol 2007;571:129-37. [CrossRef]
  • Pertwee RG. Elevating endocannabinoid levels: pharmacological strate- gies and potential therapeutic applications. Proc Nutr Soc 2014;73:96- 105. [CrossRef]
  • Maione S, Costa B, Di Marzo V. Endocannabinoids: a unique opportuni- ty to develop multitarget analgesics. Pain 2013;154:S87-93. [CrossRef]
  • Piscitelli F, Di Marzo V. “Redundancy” of Endocannabinoid Inactiva- tion: New Challenges and Opportunities for Pain Control. ACS Chem Neurosci 2012;3:356-63. [CrossRef]
  • Naidu PS, Kinsey SG, Guo TL, Cravatt BF, Lichtman AH. Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase. J Phar- macol Exp Ther 2010;334:182-90. [CrossRef]
  • Caprioli A, Coccurello R, Rapino C, Di Serio S, Di Tommaso M, Vertechy M, et al. The novel reversible fatty acid amide hydrolase in- hibitor ST4070 increases endocannabinoid brain levels and counteracts neuropathic pain in different animal models. J Pharmacol Exp Ther 2012;342:188-95. [CrossRef]
  • Huggins JP, Smart TS, Langman S, Taylor L, Young T. An efficient ran- domised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocan- nabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain 2012;153:1837-46. [CrossRef]
  • Fowler CJ, Naidu PS, Lichtman A, Onnis V. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1. Brit J Pharmacol 2009;156:412-9. [CrossRef]
  • Morera E, De Petrocellis L, Morera L, Moriello AS, Ligresti A, Nalli M, et al. Synthesis and biological evaluation of piperazinyl carba- mates and ureas as fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channel dual ligands. Bioorg Med Chem Lett 2009;19:6806-9. [CrossRef]
  • Costa B, Bettoni I, Petrosino S, Comelli F, Giagnoni G, Di Marzo V. The dual fatty acid amide hydrolase/TRPV1 blocker, N-arachidonoyl- serotonin, relieves carrageenan-induced inflammation and hyperalgesia in mice. Pharmacol Res 2010;61:537-46. [CrossRef]
  • Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG, et al. Chronic monoacylglycerol lipase blockade causes functional an- tagonism of the endocannabinoid system. Nat Neurosci 2010;13:1113- U111. [CrossRef]
  • Niphakis MJ, Johnson DS, Ballard TE, Stiff C, Cravatt BF. O-hydroxy- acetamide carbamates as a highly potent and selective class of endo- cannabinoid hydrolase inhibitors. ACS Chem Neurosci 2012;3:418-26. [CrossRef]
  • Fu J, Bottegoni G, Sasso O, Bertorelli R, Rocchia W, Masetti M, et al. A catalytically silent FAAH-1 variant drives anandamide transport in neurons. Nat Neurosci 2012;15:64-U82. [CrossRef]
  • Hogestatt ED, Jonsson BAG, Ermund A, Andersson DA, Bjork H, Alexander JP, et al. Conversion of acetaminophen to the bioactive N- acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. J Biol Chem 2005;280:31405-12. [CrossRef]
  • Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, et al. Endocannabinoid and serotonergic systems are needed for acetamin- ophen-induced analgesia. Pain 2008;139:190-200. [CrossRef]
  • Rogosch T, Sinning C, Podlewski A, Watzer B, Schlosburg J, Lichtman AH, et al. Novel bioactive metabolites of dipyrone (metamizol). Bioorg Med Chem 2012;20:101-7. [CrossRef]
  • Elmas P, Ulugol A. Involvement of cannabinoid CB1 receptors in the antinociceptive effect of dipyrone. J Neural Transm 2013;120:1533-8. [CrossRef]
  • Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A. The analgesic ac- tivity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. Eur J Pharmacol 2006;531:280-1. [CrossRef]
  • Escobar W, Ramirez K, Avila C, Limongi R, Vanegas H, Vazquez E. Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur J Pain 2012;16:676- 89. [CrossRef]
Toplam 55 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Ahmet Ulugöl Bu kişi benim

Yayımlanma Tarihi 7 Ağustos 2014
Yayımlandığı Sayı Yıl 2014 Cilt: 2014 Sayı: 2

Kaynak Göster

APA Ulugöl, A. (2014). The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation. Balkan Medical Journal, 2014(2), 115-120. https://doi.org/10.5152/balkanmedj.2014.13103
AMA Ulugöl A. The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation. Balkan Medical Journal. Şubat 2014;2014(2):115-120. doi:10.5152/balkanmedj.2014.13103
Chicago Ulugöl, Ahmet. “The Endocannabinoid System As a Potential Therapeutic Target for Pain Modulation”. Balkan Medical Journal 2014, sy. 2 (Şubat 2014): 115-20. https://doi.org/10.5152/balkanmedj.2014.13103.
EndNote Ulugöl A (01 Şubat 2014) The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation. Balkan Medical Journal 2014 2 115–120.
IEEE A. Ulugöl, “The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation”, Balkan Medical Journal, c. 2014, sy. 2, ss. 115–120, 2014, doi: 10.5152/balkanmedj.2014.13103.
ISNAD Ulugöl, Ahmet. “The Endocannabinoid System As a Potential Therapeutic Target for Pain Modulation”. Balkan Medical Journal 2014/2 (Şubat 2014), 115-120. https://doi.org/10.5152/balkanmedj.2014.13103.
JAMA Ulugöl A. The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation. Balkan Medical Journal. 2014;2014:115–120.
MLA Ulugöl, Ahmet. “The Endocannabinoid System As a Potential Therapeutic Target for Pain Modulation”. Balkan Medical Journal, c. 2014, sy. 2, 2014, ss. 115-20, doi:10.5152/balkanmedj.2014.13103.
Vancouver Ulugöl A. The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation. Balkan Medical Journal. 2014;2014(2):115-20.