May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Potent and Prolonged Analgesia in Intact Rabbit Cornea Using Synthetic Neurotensin Analogs
Author Affiliations & Notes
  • M. H. Heinemann
    Memorial Sloan-Kettering, New York, New York
    Surgery,
    Department of Ophthalmology, Weill Medical College, New York, New York
  • M. Rosenblatt
    Ophthalmology, University of California, Davis, Davis, California
  • E. Richelson
    Pharmacology, Psychiatry, Mayo Clinic, Jacksonville, Florida
  • G. Pasternak
    Memorial Sloan-Kettering, New York, New York
    Neurology,
  • D. Barbut
    Sarentis Corporation, New York, New York
  • Footnotes
    Commercial Relationships  M.H. Heinemann, Sarentis Corporation, C; M. Rosenblatt, Sarentis Corporation, F; E. Richelson, Sarentis Corporation, F; Sarentis Corporation, P; G. Pasternak, Sarentis Corporation, F; Sarentis Corporation, P; D. Barbut, Sarentis Corporation, E; Sarentis Corporation, P.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2557. doi:
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    • Get Citation

      M. H. Heinemann, M. Rosenblatt, E. Richelson, G. Pasternak, D. Barbut; Potent and Prolonged Analgesia in Intact Rabbit Cornea Using Synthetic Neurotensin Analogs. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2557.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Neurotensin (NT) and synthetic NT receptor agonists are non-opiate peptides that modulate pain at several levels of the neuraxis in animals and may be useful antinociceptive agents. Several stable NT analogs have been developed with potent analgesic activity in rodent models that also are active topically on the tail of mice. We have examined the topical analgesic effect of these analogs in the eye using Cochet-Bonnet esthesiometry.

Methods: : Corneal sensation (Cochet-Bonnet) was tested at baseline and following topical administration of different doses of two different stable neurotensin analogs in New Zealand rabbits with intact corneas. Blink responses to mechanical stimulation (10 and 15mm filament length) were assessed after instillation of 50 ul of solutions of the NT compounds (SAR-001 is N-methylArg, diaminobutyric acid, L-neo-Trp, tert-leu-L-Leu and SAR-002 is D-Lys, L-Pro,L-neo-Trp, tert-Leu, L-leu) at concentrations from 0.1 to 10 mg/ml. Dose response curves and duration of response were assessed. in concentrations of 0.1 to 10 mg/ml.

Results: : Both NT compounds completely abolished blink response to mechanical stimulation (Cochet-Bonnet) with similar dose-response curves. Maximal effects were achieved with concentrations as low as 0.5mg/ml within 15 minutes of administration. Duration of action ranged from 3.5 to 4 hours.

Conclusions: : Topically administered neurotensins eliminate the blink response following corneal stimulation for up to 4 hours in rabbit cornea and may have clinical potential as antinociceptive agents.

Keywords: cornea: epithelium • innervation: sensation • cornea: clinical science 
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