May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Significant Retinal and Choroidal Penetration of the Anti-Angiogenic Nicotinic Receptor Antagonist Mecamylamine Following Topical Administration in Cynomolgus Monkeys
Author Affiliations & Notes
  • H. H. Hsu
    Athenagen Inc, South San Francisco, California
    Clinical Research,
  • J. P. Cooke
    Cardiovascular Medicine, Stanford University, Stanford, California
  • X. Zhang
    Athenagen Inc, South San Francisco, California
    Pre-Clinical R & D,
  • M. Kengatharan
    Athenagen Inc, South San Francisco, California
    Pre-Clinical R & D,
  • Footnotes
    Commercial Relationships H.H. Hsu, Athenagen, Inc, E; J.P. Cooke, Athenagen Inc, I; Athenagen Inc, C; Athenagen Inc, P; X. Zhang, Athenagen Inc, E; Athenagen Inc, P; M. Kengatharan, Athenagen, Inc, E; Athenagen,Inc, P.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1775. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      H. H. Hsu, J. P. Cooke, X. Zhang, M. Kengatharan; Significant Retinal and Choroidal Penetration of the Anti-Angiogenic Nicotinic Receptor Antagonist Mecamylamine Following Topical Administration in Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1775. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract
 
Purpose:
 

To investigate whether topical (eye drop) administration of ATG003, an ophthalmic solution containing mecamylamine (MEC), a non-selective nicotinic acetylcholine (nACh) receptor antagonist with anti-angiogenic properties results in significant distribution to the retina-choroid and other ocular tissues in non-human primates.

 
Methods:
 

8 male Cynomolgus monkeys were divided into 4 groups and given topical 1% MEC ophthalmic solution (ATG003) (50uL) 3 times a day for 3 days into both eyes. Group 1 was terminated 3hrs post first dose on day 1 and Groups 2, 3 and 4 at 1, 3 and 6 hrs post-final dose on day 3. Tissues and fluids from the anterior and posterior segment of the eye and plasma were separated, snap frozen and analyzed for MEC concentration using a standard LC/MS/MS method.

 
Results:
 

These results show that MEC penetrates to the posterior segment of the eye, in particular the retina-choroid, following topical administration. MEC was undetectable in plasma suggesting that systemic effects of MEC are likely to be minimized following topical administration. The high concentration of MEC found in the sclera compared to the vitreous suggests that the agent reaches the posterior segment via a peri-scleral route. High levels found in retina-choroid after multiple topical administration suggests that the dosing interval may be increased to once or twice daily.  

 
Conclusions:
 

Topical administration of MEC, a non-selective nACh receptor antagonist with anti-angiogenic properties, penetrates to the retina-choroid in Cynomolgus monkeys. These data, together with data showing that MEC has anti-angiogenic properties and reduces laser-induced choroidal neovascularization (CNV) in a mouse model, suggest that topical MEC is an attractive non-invasive anti-angiogenic treatment for neovascular AMD.

 
Keywords: age-related macular degeneration • choroid: neovascularization • acetylcholine 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×