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A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

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Abstract

Background

Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported that topical natural ergot alkaloids ergocristine α-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to compare the effect of ergocristine, α-ergocryptine and ergocornine on the intraocular pressure and aqueous humor dynamics in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, in order to further explore the ocular actions of these compounds.

Methods

Experiments were conducted in albino ocular normotensive and hypertensive rabbits by intracameral injection of α-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined, in order to obtain dose–response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on aqueous humor dynamics.

Results

All natural ergot alkaloids tested reduced intraocular pressure in a dose-related fashion. The ocular hypotensive effect was greater in α-chymotrypsin-induced ocular hypertensive rabbits for the three compounds tested. All natural ergot alkaloids tested decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow in ocular normotensive and in α-chymotrypsin-induced ocular hypertensive rabbits.

Conclusion

Taken together, our data suggest that these compounds decrease both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final effect in ocular normotensive and in α-chymotrypsin-induced ocular hypertensive rabbits. Reductions in aqueous humor inflow observed after topical application of natural ergot alkaloids in α-chymotrypsin-induced ocular hypertensive rabbits can only be explained by a marked inhibition of active secretion of aqueous humor, since processes involved in aqueous humor formation may probably be altered after α-chymotrypsin injection.

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References

  1. Al-Sereiti MR, Quik RF, Turner P (1989) The effect of a single oral dose of pergolide on intraocular pressure and pupil diameter. Br J Clin Pharmacol 28:263–268

    PubMed  CAS  Google Scholar 

  2. Barnett N, Osborne NN (1993) The presence of serotonin (5-HT1) receptors negatively coupled to adenylate cyclase in rabbit and human iris-ciliary processes. Exp Eye Res 57:209–216

    Article  PubMed  CAS  Google Scholar 

  3. Becker B, Constant MA (1956) The facility of aqueous outflow. A comparison of tonography and perfusion measurements in vitro and in vivo. Arch Ophthalmol 55:305–312

    CAS  Google Scholar 

  4. Bronner A, Hommura S (1973) Influence de l’hydergine sur l’hydrodynamique de l’humeur aqueuse et sur la circulátion rétinienne. Med Strasbourg J 4:809–816

    CAS  Google Scholar 

  5. Coppi G (1992) Dihydroergocristine: a review of pharmacology and toxicology. Arzneimittelforschung 42:1381–1390

    PubMed  CAS  Google Scholar 

  6. Chang FW, Burke JA, Potter DE (1985) Mechanism of the ocular hypotensive action of ketanserin. J Ocul Pharmacol 1:137–147

    PubMed  CAS  Google Scholar 

  7. Chidlow G, Cupido A, Melena J, Osborne NN (2001) Flesinoxan, a 5-HT1A receptor agonist/alpha 1-adrenoceptor antagonist, lowers intraocular pressure in NZW rabbits. Curr Eye Res 23:144–153

    Article  PubMed  CAS  Google Scholar 

  8. Chidlow G, Le Corre S, Osborne, NN (1998) Localization of 5-hydroxytryptamine1A and 5-hydroxytryptamine7 receptors in rabbit ocular and brain tissues. Neuroscience 87:675–689

    Article  PubMed  CAS  Google Scholar 

  9. Chu E, Socci R, Chu TC (2004) PD128,907 induces ocular hypotension in rabbits: involvement of D2/D3 dopamine receptors and brain natriuretic peptide. J Ocul Pharmacol Ther 20:15–23

    Article  PubMed  CAS  Google Scholar 

  10. Chu T, Ogidigben, MJ, Potter, DE (1999) 8-OH-DPAT-induced ocular hypotension: sites and mechanisms of action. Exp Eye Res 6:227–238

    Article  Google Scholar 

  11. Diotavelli M, Auricchio G (1964) The effect of topically used hydergine on ocular tension. Ophthalmologica 147:448–454

    Google Scholar 

  12. Eisenlohr JE, Langham RF (1962) The relationship between pressure and volume changes in living and dead rabbit eyes. Invest Ophthalmol 1:63–67

    PubMed  CAS  Google Scholar 

  13. Elibol O, Guler C, Yuksel N (1992) The effects of dopamine, haloperidol and bromocriptine on intraocular pressure. Int Ophthalmol 16:343–347

    Article  PubMed  CAS  Google Scholar 

  14. Farahbakhsh NA, Cillufo MC (1994) Synergistic effect of adrenergic and muscarinic receptor activation of [ Ca2+] spikes and Ca2+ currents in rabbit ciliary body epithelial cells. Exp Eye Res 58:197–206

    Article  PubMed  CAS  Google Scholar 

  15. Fourman S, Fourman MB (1989) Correlation of tonography and constant pressure perfusion measurements of outflow facility in the rabbit. Curr Eye Res 9:963–969

    Google Scholar 

  16. Genée E, Geisendörfer T (1975) Blutdruckändernde Medikamente und Augeninnendruck im Tierversuch. Albrecht v Graefes Klin Exp Ophthal 95:187–194

    Article  Google Scholar 

  17. Green K (1992) Models and methods for testing toxicity of aqueous humor, iris and ciliary body. In: Hockwin O, Green K, Rubin L (eds) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart, pp 219–242

    Google Scholar 

  18. Hochgesand DH, Dunn JJ, Crook RB (2001) Catecholaminergic regulation of Na-K-Cl cotransport in pigmented ciliary epithelium: differences between PE and NPE. Exp Eye Res 72:1–12

    Article  PubMed  CAS  Google Scholar 

  19. Krootila K, Palkama A, Uusitalo H (1987) Effect of serotonin and its antagonist (ketanserin) on intraocular pressure in the rabbit. Ocul Pharmacol J 4:279–290

    Google Scholar 

  20. Mancino R, Cerulli L, Ricci A, Amenta F (1992) Direct demonstration of dopamine D1-like receptor sites in the ciliary body of the rabbit eye by light microscope autoradiography. Naunyn Schmiedebergs Arch Pharmacol 346:644–648

    Article  PubMed  CAS  Google Scholar 

  21. Melena J, Santafé J, Segarra-Doménech J, Puras G (1999) Aqueous humor dynamics in alfa chymotrypsin-induced ocular hypertensive rabbits. J Ocul Pharmacol Ther 15:19–26

    PubMed  CAS  Google Scholar 

  22. Melena J, Santafé J, Segarra-Doménech J (1998) The effect of topical dihydroergocristine on the intraocular pressure in chymotrypsin-induced ocular hypertensive rabbits. Meth Find Exp Clin Pharmacol 20:861–867

    Article  CAS  Google Scholar 

  23. Mito T, Delamere NA, Coca-Prados M (1993) Calcium-dependent regulation of cation transport in cultured human nonpigmented ciliary epithelial cells. Am J Physiol 33:519–525

    Google Scholar 

  24. Neufeld AH, Page ED (1977) In vitro determination of the ability of drugs to bind to adrenergic receptors. Invest Ophthalmol Vis Sci 16:1118–1124

    PubMed  CAS  Google Scholar 

  25. Ohuchi T, Yoshimura N, Tanihara H, Kuriyama S, Ito S, Honda Y (1992) Ca2+ mobilization in nontransformed ciliary nonpigmented epithelial cells. Invest Ophtalmol Vis Sci 33:1696–1705

    PubMed  CAS  Google Scholar 

  26. Osborne NN, Wood JP, Melena J, Chao HM, Nash MS, Bron AJ, Chidlow G (2000) 5-Hydroxytryptamine1A agonists: potential use in glaucoma. Evidence from animal studies. Eye 14:454–463

    PubMed  Google Scholar 

  27. Peroutka SJ (1996) Drugs effective in the therapy of migraine. In: Hambard JG, Limbird LE (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 9th edn. McGraw Hill, New York, pp 487–502

    Google Scholar 

  28. Potter DE (1981) Adrenergic pharmacology of aqueous humor dynamics. Pharmacol Rev 33:133–153

    PubMed  CAS  Google Scholar 

  29. Potter DE, Ogidigben MJ, Chu TC (1998) Lisuride acts at multiple sites to induce ocular hypotension and mydriasis. Pharmacology 57:249–260

    Article  PubMed  CAS  Google Scholar 

  30. Potter DE, Shumate DJ (1987) Cianergoline lowers intraocular pressure in rabbits and monkeys and inhibits contraction of the cat nictitans by suppressing sympathetic neuronal function. J Ocul Pharmacol 3:309–321

    Article  PubMed  CAS  Google Scholar 

  31. Potter DE, Burke JA (1982) Effects of ergoline derivatives on intraocular pressure and iris function in rabbits an monkeys. Curr Eye Res 2:281–288

    PubMed  Google Scholar 

  32. Prunte C, Nuttli I, Markstein R, Kohler C (1997) Effects of dopamine D-1 and D-2 receptors on intraocular pressure in conscious rabbits. J Neural Transm 104:111–123

    Article  PubMed  CAS  Google Scholar 

  33. Puras G, Santafé J, Segarra, J, Melena J (2002) Effects of topical natural ergot alkaloids on intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits. J Ocul Pharmacol Ther 18:41–52

    Article  PubMed  CAS  Google Scholar 

  34. Puras G, Santafe J, Segarra J, Garrido M, Melena J (2002) The effect of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in rabbits with alpha-chymotrypsin-induced ocular hypertension. Graefes Arch Clin Exp Ophthalmol 240:322–328

    Article  PubMed  CAS  Google Scholar 

  35. Quigley HA, Broman AT (2006) The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 90:262–267

    Article  PubMed  CAS  Google Scholar 

  36. Rintelen F, Smolik H (1950) Über den Einfluss des Hydergins auf den intraokularen and diastolischen Zentralarteriendruck. Ophthalmologica 120:100–103

    PubMed  CAS  Google Scholar 

  37. Roquebert J, Demichel P (1987) Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol 1:23–33

    Article  PubMed  CAS  Google Scholar 

  38. Rowell PP, Larson BT (1999) Ergocryptine and other ergot alkaloids stimulate the release of [3H]dopamine from rat striatal synaptosomes. J Anim Sci 77:1800–1806

    PubMed  CAS  Google Scholar 

  39. Rowland JM, Potter DE, Reiter RJ (1981) Circadian rhythm in intraocular pressure: a rabbit model. Curr Eye Res 1:169–173

    PubMed  CAS  Google Scholar 

  40. Santafé J, Segarra J, Garrido M, Pablo V (1991) Effects of topical dihydroergocristine on intraocular pressure, aqueous humor dynamics and pupil diameter in conscious rabbits. A comparative study with timolol and pilocarpine. Meth Find Exp Clin Pharmacol 13:231–238

    Google Scholar 

  41. Savolainen J, Rautio J, Razzetti R, Jarvinen T (2003) A novel D2-dopaminergic and alpha2-adrenoceptor receptor agonist induces substantial and prolonged IOP decrease in normotensive rabbits. J Pharm Pharmacol 55:789–794

    Article  PubMed  CAS  Google Scholar 

  42. Siegel MJ, Lee PY, Podos SM, Mittag TW (1987) Effect of topical ergolide on aqueous dynamics in normal and glaucomatous monkeys. Exp Eye Res 44:227–233

    Article  PubMed  CAS  Google Scholar 

  43. Simkova M, Zahn K (1952) The effect of hydergine on retinal circulation. Ophthalmologica 124:39–49

    Article  PubMed  CAS  Google Scholar 

  44. Steinbach PD, Bell H (1977) Wirkung gefäserweiternder Substanzen auf Augeninnendruck und Blutdruck. Albrecht v Graefes Arch Klin Exp Ophthal 202:213–222

    Article  CAS  Google Scholar 

  45. Sugrue MF (1997) New approaches to antiglaucoma therapy. J Med Chem 40(18):2793–2809

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research work has been carried out with funds from the Universidad del País Vasco (Spain). G. Puras and J. Melena were supported by fellowships from the Universidad del País Vasco and the Gobierno Vasco (Spain) respectively.

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Authors and Affiliations

  1. Department of Pharmacology, Universidad Autónoma de Tamaulipas, Tamaulipas, Mexico

    Gustavo Puras

  2. Department of Pharmacology, Faculty of Pharmacy, Universidad del País Vasco, Vitoria, Spain

    Juan Santafé, José Segarra, Manuel Garrido & José Melena

  3. Universidad Autónoma de Tamaulipas, Carretera Sendero Nacional Km 3., H-Matamoros, Tamaulipas, Mexico, 87349

    Gustavo Puras

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  1. Gustavo Puras
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  2. Juan Santafé
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Correspondence to Gustavo Puras.

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Puras, G., Santafé, J., Segarra, J. et al. A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits. Graefes Arch Clin Exp Ophthalmol 245, 1559–1567 (2007). https://doi.org/10.1007/s00417-007-0596-3

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