Skip to main content
SpringerLink
Log in

Use of Cevimeline, a Muscarinic Ml and M3 Agonist, in the Treatment of Sjögren’s Syndrome

  • Chapter
Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 506))

Abstract

Sjögren’s syndrome (SS) is characterized by symptoms of dryness of the eyes and mouth associated with lymphoid infiltrates of the lacrimal and salivary glands. Confusion exists about the criteria for diagnosis of this disease, 1 but the frequency, according to a newly proposed international criterion that requires either a characteristic minor salivary gland biopsy or the presence of an antibody against SS-A/SS-B antigen, 2 is about 0.5% of adult women. SS may exist with other autoimmune disorders (secondary SS associated with rheumatoid arthritis, systemic lupus erythematosus or scleroderma), or as a primary condition. Primary and secondary SS are systemic autoimmune disorders, although the most recognizable manifestations are the ocular and oral components of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Fox, R., Classification Criteria for Sjogren’s syndrome. Rheumatic Disease Clinics of North America: Current Controversies in Rheumatology, 1994. 20: p. 391–407.

    CAS  Google Scholar 

  2. Vitali, C. and S. Bombardieri, The Europian classification criteria for Sjogren’s syndrome (SS): proposal for modification of the rules for classification suggested by the analysis of the receiver operating characteristic (ROCS) curve of the criteria performance. J. Rheum, 1997. 24 (supplement): p. S18.

    Google Scholar 

  3. Nelson, J.D., Diagnosis of keratoconjunctivitis sicca. Int Ophthalmol Clin, 1994. 34(1): p. 37–56.

    Article  CAS  PubMed  Google Scholar 

  4. Watanabe, H., et al., Human corneal and conjunctival epithelia produce a mucin-like glycoprotein for the apical surface. Invest Ophthalmol Vis Sci, 1995. 36(2): p. 337–44.

    CAS  PubMed  Google Scholar 

  5. Fox, R.I., M. Stern, and P. Michelson, Update in Sjogren syndrome [In Process Citation]. Curt Opin Rheumatol, 2000. 12(5): p. 391–8.

    Article  CAS  Google Scholar 

  6. Lemp, M.A., Tear film: new concepts and implications for the management of the dry eye. Trans New Orleans Acad Ophthalmol, 1987. 35: p. 53–64.

    CAS  PubMed  Google Scholar 

  7. Fox, R.I. et al., Evolving concepts of diagnosis, pathogenesis, and therapy of Sjogren’s syndrome. Curr Opin Rheumatol, 1998. 10(5): p. 446–56.

    Article  CAS  PubMed  Google Scholar 

  8. Stern, M.E., et al., A unified theory of the role of the ocular surface in dry eye. Adv Exp Med Biol, 1998.438: p. 643–51.

    Article  CAS  PubMed  Google Scholar 

  9. Andoh, Y., et al., Morphometric analysis of secretory glands in Sjögren’s syndrome. Am Rev Respir Dis, 1993. 148(5): p. 1358–62.

    Article  CAS  PubMed  Google Scholar 

  10. Daniels, T.E. and J.P. Whitcher, Association of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca. Analysis of 618 patients with suspected Sjogren’s syndrome. Arthritis Rheum, 1994. 37(6): p. 869–77.

    Article  CAS  PubMed  Google Scholar 

  11. Kovacs, L., et al., Impaired microvascular response to cholinergic stimuli in primary Sjogren’s syndrome. Ann Rheum Dis, 2000. 59(1): p. 48–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Main, C., P. Blennerhassett, and S.M. Collins, Human recombinant interleukin 1 beta suppresses acetylcholine release from rat myenteric plexus. Gastroenterology, 1993. 104(6): p. 1648–54.

    Article  CAS  PubMed  Google Scholar 

  13. Quirion, R., et al., Growth factors and lymphokines: modulators of cholinergic neuronal activity. Can J Neurol Sci, 1991. 18(3 Suppl): p. 390–3.

    Article  CAS  PubMed  Google Scholar 

  14. Bacman, S.R., et al., Human primary Sjogren’s syndrome autoantibodies as mediators of nitric oxide release coupled to lacrimal gland muscarinic acetylcholine receptors. Curr Eye Res, 1998. 17(12): p. 1135–42.

    Article  CAS  PubMed  Google Scholar 

  15. Waterman, S.A., T.P. Gordon, and M. Rischmueller, Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjogren’s syndrome. Arthritis Rheum, 2000. 43(7): p. 1647–54.

    Article  CAS  PubMed  Google Scholar 

  16. Kong, L., et al., Fas and Fas ligand expression in the salivary glands of patients with primary Sjogren’s syndrome. Arthritis Rheum, 1997. 40(1): p. 87–97.

    Article  CAS  PubMed  Google Scholar 

  17. Liu, X.B., et al., G-protein signaling abnormalities mediated by CD95 in salivary epithelial cells. Cell Death Differ, 2000. 7(11): p. 1119–1126.

    Article  CAS  PubMed  Google Scholar 

  18. Tominaga, M., et al., Expression of metalloproteinase-2 (gelatinase A) in labial salivary glands of patients with Sjogren’s syndrome with HTLV-I infection. Clin Exp Rheumatol, 1999. 17(4): p. 463–6.

    CAS  PubMed  Google Scholar 

  19. Azuma, M., et al., Suppression of tumor necrosis factor alpha-induced matrix metalloproteinase 9 production by the introduction of a super-repressor form of inhibitor of nuclear factor kappaBalpha complementary DNA into immortalized human salivary gland acinar cells. Prevention of the destruction of the acinar structure in Sjogren’s syndrome salivary glands. Arthritis Rheum, 2000. 43(8): p. 1756–67.

    Article  CAS  PubMed  Google Scholar 

  20. Laurie, G.W., et al., Immunological and partial sequence identity of mouse BM180 with wheat alphagliadin. Biochem Biophys Res Commun, 1995.217(1): p. 10–5.

    Article  CAS  PubMed  Google Scholar 

  21. Pflugfelder, S.C., et al.,Conjunctival cytologic features of primary Sjogren’s syndrome. Ophthalmology, 1990. 97(8): p. 985–91.

    Article  CAS  PubMed  Google Scholar 

  22. Jones, D.T., et al., Alterations of ocular surface gene expression in Sjogren’s syndrome. Adv Exp Med Biol, 1998. 438: p. 533–6.

    Article  CAS  PubMed  Google Scholar 

  23. Marsh, P. and S.C. Pflugfelder, Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology, 1999. 106(4): p. 811–6.

    Article  CAS  PubMed  Google Scholar 

  24. Liu, Z., et al., Increased expression of the type I growth factor receptor family in the conjunctival epithelium of patients with keratoconjunctivitis sicca. Am J Ophthalmol, 2000. 129(4): p. 472–480.

    Article  CAS  PubMed  Google Scholar 

  25. Baumgold, J., et al., Comparison of second-messenger responses to muscarinic receptor stimulation in M1-transfected A9 L cells. Cell Signal, 1995. 7(1): p. 39–43.

    Article  CAS  PubMed  Google Scholar 

  26. Laurie, G., et al., BM180: a novel basement membrane protein with a role in stimulus secretion coupling by lacrimal acinar cells. Am. J. Physiol, 1996. 39: p. C1743–C1750.

    Google Scholar 

  27. Wu, A., et al., Effect of tumor necrosis factor alpha and interferon gamma on the growth of a human salivary gland cell line. J. Cell Physiol, 1994. 161: p. 217–226.

    Article  CAS  PubMed  Google Scholar 

  28. Wu, A.J., et al., Modulation of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by interferon-gamma in a human salivary gland cell line. J Cell Physiol, 1997. 171(2): p. 117–24.

    Article  CAS  PubMed  Google Scholar 

  29. Cheresh, D.A., J. Leng, and R.L. Klemke, Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells. J Cell Biol, 1999. 146(5): p. 1107–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Eva, C., J.L. Meek, and E. Costa, Vasoactive intestinal peptide which coexists with acetylcholine decreases acetylcholine turnover in mouse salivary glands. J Pharmacol Exp Ther, 1985. 232(3): p. 670–4.

    CAS  PubMed  Google Scholar 

  31. Yamamoto, H., et al., Detection of alterations in the levels of neuropeptides and salivary gland responses in the non-obese diabetic mouse model for autoimmune sialoadenitis. Scand J Immunol, 1997. 45(1): p. 55–61.

    Article  CAS  PubMed  Google Scholar 

  32. Humphreys-Beher, M.G. and A.B. Peck, New concepts for the development of autoimmune exocrinopathy derived from studies with the NOD mouse model. Arch Oral Biol, 1999. 44 Suppl 1: p. S21–5.

    Article  PubMed  Google Scholar 

  33. Robinson, C.P., et al., Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren’s syndrome. Proc Natl Acad Sci U S A, 1998. 95(13): p. 7538–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dawson, L.J., S.E. Christmas, and P.M. Smith, An investigation of interactions between the immune system and stimulus-secretion coupling in mouse submandibular acinar cells. A possible mechanism to account for reduced salivary flow rates associated with the onset of Sjogren’s syndrome. Rheumatology (Oxford), 2000. 39(11): p. 1226–33.

    Article  CAS  Google Scholar 

  35. Wotta, D.R., et al., MI, M3 and M5 muscarinic receptors stimulate mitogen-activated protein kinase. Pharmacology, 1998. 56(4): p. 175–86.

    Article  CAS  PubMed  Google Scholar 

  36. Lu, G., et al., Tumor necrosis factor-alpha and interleukin-1 induce activation of MAP kinase and SAP kinase in human neuroma fibroblasts. Neurochem Int, 1997. 30(4–5): p. 401–10.

    Article  CAS  PubMed  Google Scholar 

  37. Fisher, A., et al., (+-)-cis-2-methyl-spiro(I,3-oxathiolane-5,3’) quinuclidine (AF102B): a new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats. Neurosci Lett, 1989. 102(2–3): p. 325–31.

    Article  CAS  PubMed  Google Scholar 

  38. Fisher, A., Therapeutic strategies in Alzheimer’s disease: M1 muscarinic agonists. Jpn J Pharmacol, 2000. 84(2): p. 101–12.

    Article  CAS  PubMed  Google Scholar 

  39. Iga, Y., et al., (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3’-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions in rats and mice: the role of muscarinic acetylcholine receptors. Jpn J Pharmacol, 1998. 78(3): p. 373–80.

    Article  CAS  PubMed  Google Scholar 

  40. Fox, R., et al., Randomized,placebo controlled trial of SNI-2011, a novel M3 muscarinic receptor agonist, for the treatment of Sjogrenn’s syndrome. Arth Rheum, 1998. 41 (supplement): p. S288.

    Google Scholar 

  41. Masunaga, H., et al Long-lasting salivation induced by a novel muscarinic receptor agonist SNI-2011 in rats and dogs. Eur J Pharmacol, 1997. 339(1): p. 1–9.

    Article  CAS  PubMed  Google Scholar 

  42. Iwabuchi, Y. and T. Masuhara, Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: identification of a potential therapeutic agent for treatment of Sjorgen’s syndrome. Gen Pharmacol, 1994. 25(1): p. 123–9.

    Article  CAS  PubMed  Google Scholar 

  43. Iwabuchi, Y., M. Katagiri,.and T. Masuhara, Salivary secretion and histopathological effects after single administration of the muscarinic agonist SNI-2011 in MRL 1pr mice. Arch Int Pharmacodyn Ther, 1994. 328(3): p. 315–25.

    CAS  PubMed  Google Scholar 

  44. Nagler, R.M., D. Laufer, and A. Nagler, Parotid gland dysfunction in an animal model of chronic graft-vs-host disease. Arch Otolaryngol Head Neck Surg, 1996. 122(10): p. 1057–60.

    Article  CAS  PubMed  Google Scholar 

  45. Fisher, A., et al., Selective signaling via unique MI muscarinic agonists. Ann N Y Acad Sci, 1993. 695: p. 300–3.

    Article  CAS  PubMed  Google Scholar 

  46. Leloup, C., et al., M1 muscarinic receptors block caspase activation by phosphoinositide 3-kinase-and MAPK/ERK-independent pathways. Cell Death Differ, 2000. 7(9): p. 825–33.

    Article  CAS  PubMed  Google Scholar 

  47. Fox, P.C., et al., Pilocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia). Arch Intern Med, 1991. 151(6): p. 1149–52.

    Article  CAS  PubMed  Google Scholar 

  48. Greenspan, D. and T.E. Daniels, Effectiveness of pilocarpine in postradiation xerostomia. Cancer, 1987. 59: p. 1123–1125.

    Article  CAS  PubMed  Google Scholar 

  49. Johnson, J.T., et al., Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer [see comments]. N Engl J Med, 1993. 329(6): p. 390–5.

    Article  CAS  PubMed  Google Scholar 

  50. Vivino, F.B., et al., Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized,placebo-controlled, fixed-dose, multicenter trial. P92–01 Study Group [In Process Citation]. Arch Intern Med, 1999. 159(2): p. 174–81.

    Article  CAS  PubMed  Google Scholar 

  51. Fox, R., et al., Randomized,placebo controlled trial of SNI-2011, a novel M3 muscarinic receptor agonist, for the treatment of Sjogrenn’s syndrome. Arth Rheum, 1998.41 (supplement): p. S288.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy and Rheumatology Clinic Scripps Memorial Hospital and Research Foundation La Jolla, California, USA

    Robert I. Fox

Authors
  1. Robert I. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Schepens Eye Research Institute, Boston, Massachusetts, USA

    David A. Sullivan , Darlene A. Dartt  & Rose M. Sullivan ,  & 

  2. Harvard Medical School, Boston, Massachusetts, USA

    David A. Sullivan  & Darlene A. Dartt  & 

  3. Allergan, Inc., Irvine, California, USA

    Michael E. Stern

  4. Tokyo Dental College, Chiba, Japan

    Kazuo Tsubota

  5. Ichikawa General Hospital, Chiba, Japan

    Kazuo Tsubota

  6. University of New Orleans, New Orleans, Louisiana, USA

    B. Britt Bromberg

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic/Plenum Publishers

About this chapter

Cite this chapter

Fox, R.I. (2002). Use of Cevimeline, a Muscarinic Ml and M3 Agonist, in the Treatment of Sjögren’s Syndrome. In: Sullivan, D.A., Stern, M.E., Tsubota, K., Dartt, D.A., Sullivan, R.M., Bromberg, B.B. (eds) Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3. Advances in Experimental Medicine and Biology, vol 506. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0717-8_155

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0717-8_155

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5208-2

  • Online ISBN: 978-1-4615-0717-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation