Manuscript Number : IJSRST151514

OPIOID Pharmacology : A Review

Authors(6) :-Vivek Sharma, Sunil Dutt, Rahul Kumar, Pankaj Sharma, Athar Javed, Rajender Guleria

Pain is an unpleasant sensation that originates from ongoing or impending tissue damage. Management of different types of pain (acute, postoperative, inflammatory, neuropathicor cancer) is challenging and yet the most frequent issue encountered by clinicians. Pharmacological therapy is the first line of approach for the treatment of pain and opioid drugs are prescribed for acute and chronic pain of moderate/severe intensity arising from malignant and non-malignant diseases. The opium poppy was cultivated as early as 3400BC in Mesopotamia. The term opium refers to a mixture of alkaloids from the poppy seed. Opiates are naturally occurring alkaloids such as morphine or codeine and opioid is the term used broadly to describe all compounds that work at the opioid receptors. The physiologic modulation of noxious stimuli involves a highly complex system that integrates the actions of multiple opioid receptors and endogenous opioid peptides. Opioids produce their actions at a cellular level by activating opioid receptors. These receptors are distributed throughout the central nervous system (CNS) with high concentrations in the nuclei of tractus solitarius, peri-aqueductal grey area (PAG), cerebral cortex, thalamus and substantia gelatinosa (SG) of the spinal cord. They have also been found on peripheral afferent nerve terminals and many other organs. The efficacy of centrally applied opioids is well recognized, but when applied peripherally, for example in post-traumatic and inflammatory states, their actions are less reliable. Although they are associated with addiction, dependence, tolerance and abuse liability even then their place in pain management remains undebatable and unchallenged.

Authors and Affiliations

Vivek Sharma
Department of Pharmacology, Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India
Sunil Dutt
Department of Pharmacology, Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India
Rahul Kumar
Department of Pharmacology, Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India
Pankaj Sharma
Department of Pharmacology, Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India
Athar Javed
Department of Pharmacology, Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India
Rajender Guleria

Endorphins, Morphine , Opoids, Pain

  1. Strohbuecker B et al. Pain prevalence in hospitalized patients in a Germanuniversity teaching hospital. J Pain Symptom Manage. 2005; 29(5):498-506.
  2. Yates P et al. The prevalence and perception of pain amongst hospital in-patients. J Clin Nurs 1998; 7(6):521-30.
  3. Goldberg DS and McGee SJ. Pain as a global public health priority. BMC Public Health2011;11: 770.
  4. Gavril W P and Ying-Xian Pan. Mu Opioids and Their Receptors: Evolution of a Concept. Pharmacol Rev.2013;65:1257-1317.
  5. Martin WR.Opioid antagonists. Pharmacol Rev.1967;19:463-521.
  6. Macht DI. The history of opium and some its preparations and alkaloids.JAMA.1915;477-481.
  7. Gates M and Tschudi G. The synthesis of morphine. J Am Chem Soc.1956;78: 1380-1393.
  8. Reisine T and Pasternak GW. Opioid analgesics and antagonists, in Goodman& Gilman's: The Pharmacological Basis of Therapeutics (Hardman JG and LimbirdLE, eds, ed).1996;521-556, McGraw-Hill, New York.
  9. McDonald J, Lambert DG. Opioid receptors; Continuing Education in Anaesthesia, Critical Care & Pain.2005;5(1):22-25
  10. Pert A and Yaksh TL. Sites of morphine induced analgesia in the primatebrain: relation to pain pathways. Brain Res.1974; 80:135-140.
  11. Simon EJ, Hiller JM, and Edelman I. Stereospecific binding of the potentnarcotic analgesic ( 3 H) Etorphine to rat-brain homogenate. Proc Natl Acad SciUSA.1973;70:1947-1949.
  12. Goldstein A, Lowney LI and Pal BK. Stereospecific and nonspecific inter-actions of the morphine congener levorphanol in subcellular fractions of mousebrain. Proc Natl Acad Sci USA.1971; 68:1742-1747
  13. Hughes J, Smith TW, Kosterlitz HW et al. Identification of Two RelatedPentapeptides from the Brain with Potent Opiate Agonist Activity.Nature. 1975 ; 258:577-580.
  14. Mansour A, Watson SJ. In Handbook of ExperimentalPharmacology 104/1; Herz, A.; Akil, H.; Simon, E.J.; Eds.;Springer: Berlin, 1993;79-105.
  15. Anna Janecka, Jakub Fichna and Tomasz Janecki. Opioid Receptors and their Ligands. Current Topics in Medicinal Chemistry. 2004; 4: 1-17
  16. Shang Y, Filizola M. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling. Eur J Pharmacol. (2015), http://dx.doi.org/10.1016/j.ejphar.2015.05.012i
  17. Tripathi KD. Opioid Analgesics andAntagonists. In Essentials of Medical Pharmacology, 6 th Edition, Jaypee Brothers.2008; 462-464.
  18. Koneru A, Sreemantula Satyanarayana and Shaik Rizwan; Endogenous Opioids: Their Physiological Role and Receptors;Global Journal of Pharmacology.2009.3 (3): 149-153.
  19. Trescot AM, Sukdeb D, Marion Lee and Hans Hansen. Opioid Pharmacology. Pain Physician. 2008;11: 133-153.
  20. Snyder B. Revisiting old friends: update on opioid pharmacology.Aust Prescr. 2014;37:56-60.
  21. Miyatake M et al., Inhibition of EGF-induced ERK/MAP kinase-mediated astrocyte proliferation by mu opioids: integration of G protein and beta-arrestin 2-dependent pathways. J Neurochem. 2009; 110(2):662-74.
  22. Raman M, Chen W and Cobb MH. Differential regulation and properties of MAPKs. Oncogene. 2007;26(22):3100-12.
  23. Schwindinger WF et al. Synergistic roles for G-protein gamma3 and gamma7 subtypes in seizure susceptibility as revealed in double knock-out mice. J Biol Chem. 2012; 287(10):7121-33.
  24. Murga C et al. Activation of Akt/protein kinase B by G protein-coupled receptors. Arole for alpha and beta gamma subunits of heterotrimeric G proteins acting through phosphatidylinositol-3-OH kinasegamma. J Biol Chem. 1998;273(30):19080-5.
  25. Tegeder I and Geisslinger G.Opioids as modulators of cell death and survival--unraveling mechanisms and revealing new indications. Pharmacol Rev. 2004;56(3):351-69.
  26. Sharp BM. Multiple opioid receptors on immune cells modulate intracellular signaling. Brain Behav Immun. 2006; 20(1):9-14.
  27. Sacerdote P E et al. Experimental evidence for immunomodulatory effects of opioids. Adv Exp Med Biol. 2003; 521: 106-16.
  28. Pathan H and Williams J. Basic opioid pharmacology: an update; British Journal of Pain. 2012; 6(1):11-16.
  29. Gilman A, Rall J, Nies A and Taylor P., eds. The Pharmacological Basis of Therapeutics. New York: Pergamon Press, 1990.
  30. Pert C and Snyder SH. Opiate receptor: Demonstration in nervous tissue. Science. 1973;179:1011-1014.
  31. Stone LS, Fairbanks CA, Laughlin TM et al. Spinal analgesicactions of the new endogenous opioid peptides endomorphin-1 and -2. Neuroreport 1997;8:3131-5.
  32. Goldberg IE Rossi GC, Letchworth SR, et al. Pharmacologicalcharacterization of endomorphin-1 andendomorphin-2 in mouse brain. J Pharmacol Exp Ther. 1998;286:1007-13.
  33. Simon E. Opioid receptors and endogenous opioid peptides. Med Res Rev.1991;11:357-374.
  34. Khachaturian H, Lewis M and Watson SJ. Enkephalin systems indiencephalon and brainstem ofrat. J Comp Neurol.1983; 220:310-320.
  35. Chapman CL and JM De Castro. Running addiction: measurement and associatedpsychological characteristics. Journal of Sports Medicine and Physical Fitness.1990; 30: 283-290.
  36. Sprenger T A, BertheleS, Platzer H, Boecker and Tolle TR. What to learn from in vivo opioidergic brain imaging? European Journal of Pain.2005; 9: 117-121
  37. Przew ocki R. Some aspects of physiology andpharmacology of endogenous opioid peptides. Polish J. Pharmacol. Pharmacy.1984; 36(2-3): 137-58.
  38. Dalayeun JF, Nor's JM and Bergal S. Physiology of beta-endorphins. A close-up view and a review of the literature. Biomed Pharmacotherapeutics. 1993; 47(8): 311-20.
  39. Comb M, Seeburg PH et al. Primary structure of the human Met-and Leu-enkephalin precursor and its mRNA.Nature.1982; 295: 663-666.
  40. Day R C, Lazure A, Basak A et al.Prodynorphin processing by proprotein convertase2. Cleavage at single basic residues and enhanced processing in the presence of carboxypeptidase activity. J. Biol. Chem.1998;273(2): 829-36.
  41. Gutstein H, Akil H. Opioid analgesics. In: Brunton L, Lazo L, ParkerK, eds. Goodman & Gilman's the pharmacological basis of therapeutics,11th ed. New York, NY: McGraw-Hill, 2005:547-590.
  42. Gulland JM, Robinson R. The Morphine Group. Part I. ADiscussion of the Constitutional Problem. J. Chem. Soc. 1923;123: 980-998.
  43. Takemori AE, Portoghese PS. Evidence for the Interaction ofMorphine with Kappa and Delta Opioid Receptors to InduceAnalgesia in Beta-funaltrexamine-treated Mice. J. Pharmacol. Exp. Ther. 1987; 243: 91-94.
  44. Blumberg H, Dayton HB. Naloxone, Naltrexone, and RelatedNoroxymorphones. Adv. Biochem. Psychopharmacol. 1973;8:33- 43.
  45. Leslie FM. Methods Used for the Study of Opioid Receptors. Pharmacol. Rev. 1987;39:197-249.
  46. Magnan J, PatersonSJ et al. TheBinding Spectrum of Narcotic Analgesic Drugs with Different Agonist and Antagonist Properties. Naunyn. Schmiedebergs. Arch. Pharmacol. 1982:319:197-205.
  47. Berezniuk I and Fricker LD. Endogenous opioids, in The Opiate Receptors(Pasternak GW, ed, ed).2011;93-120, Springer, New York.
  48. Hoellt V. Multiple Endogenous Opioid Peptides. Trends in Neuroscience. 1983;6; 24-26.
  49. Teschemacher H. In Handbook of experimentalPharmacology 104/1; Herz, A.; Akil, H.; Simon, E.J.; Eds., Springer, Berlin.1993; 499-528.
  50. Brantl V, Teschemacher H et al. NovelOpioid Peptides Derived From Casein (beta-Casomorphins). I.Isolation from Bovine Casein Peptone. Hoppe-Seyler's Z. Physiol. Chem. 1979;360;1211-1216.
  51. Ross FB and Smith MT. The intrinsic antinociceptive effects of oxycodone appear to be k -opioid receptor mediated. Pain.1997;73:151-157.
  52. Thomas JM and James CE. Parmacology of Opioid and Nonopioid Analgesics in Chronic Pain States ; JPET.2001; 299:811-817.
  53. Joshi GP. Sufentanil for chronic pain management. FutNeurol.2010; 5: 791-6.
  54. Strain EC, Walsh SL, Preston KL, Liebson IA, Bigelow GE. The effects of buprenorphine in buprenorphine-maintainedvolunteers. Psychopharmacology (Berl). 1997; 129: 329-38.
  55. Poklis A. Fentanyl: a review for clinical and analytical toxicologists. J Toxicol Clin Toxicol. 1995; 33: 439-47.
  56. Kharasch ED, Hoffer C, Altuntas TG, Whittington D.Quinidine as a probe for the role of p-glycoprotein in theintestinal absorption and clinical effects of fentanyl. J Clin Pharmacol. 2004; 44: 224-33.
  57. Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics ofopioids. Clin Pharmacol Ther 2007; 81: 429-44.
  58. Asbjrn MD, Rasmus DJ et al. Differences between opioi s:pharmacological,experimental, clinical and economical perspectives. British Journal of ClinicalPharmacology. 2012;75:1:60-78.
  59. Wandel C, Kim R, Wood M, Wood A. Interaction ofmorphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology. 2002; 96: 913-20.
  60. Rodriguez M, Ortega I, Soengas I, Suarez E, Lukas JC,Calvo R. Effect of P-glycoprotein inhibition on methadoneanalgesia and brain distribution in the rat. J Pharm Pharmacol. 2004; 56: 367-74.
  61. Osborne R, Joel S, Grebenik K, Trew D, Slevin M. Thepharmacokinetics of morphine and morphine glucuronides in kidney failure. Clin Pharmacol Ther 1993; 54: 158-67.
  62. Dr mahesh trivedi, dr shafee shaikh,dr carl gwinnutt. Pharmacology of opioids part 1anaesthesia tutorial of the week 64;atotw 64 pharmacology of opioids -part 1 12/08/2007;1-7

Publication Details

Published in : Volume 1 | Issue 5 | November-December 2015
Date of Publication : 2015-12-25
License:  This work is licensed under a Creative Commons Attribution 4.0 International License.
Page(s) : 01-11
Manuscript Number : IJSRST151514
Publisher : Technoscience Academy

Print ISSN : 2395-6011, Online ISSN : 2395-602X

Cite This Article :

Vivek Sharma, Sunil Dutt, Rahul Kumar, Pankaj Sharma, Athar Javed, Rajender Guleria, " OPIOID Pharmacology : A Review ", International Journal of Scientific Research in Science and Technology(IJSRST), Print ISSN : 2395-6011, Online ISSN : 2395-602X, Volume 1, Issue 5, pp.01-11, November-December-2015.
Journal URL : http://ijsrst.com/IJSRST151514

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