Elsevier

Life Sciences

Volume 63, Issue 24, 6 November 1998, Pages 2181-2188
Life Sciences

Effect of the CB1 receptor antagonist, SR141716A, on cannabinoid-induced ocular hypotension in normotensive rabbits

https://doi.org/10.1016/S0024-3205(98)00499-8Get rights and content

Abstract

The present study attempts to indirectly determine if a neuronal cannabinoid (CB1) receptor mediates the intraocular pressure (IOP) reduction effects of arachidonoyl ethanolamide (AEA), its R-alpha-isopropyl analog, and the non-classical cannabinoid, CP-55,940. A series of these cannabinoids were dissolved in an aqueous 10–20% 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD) solution (containing 3% polyvinyl alcohol) and administered (25–62.5 μg) unilaterally to normotensive rabbit eyes. This was repeated on animals pre-treated with a subcutaneous injection (2.5 mg/kg) of the highly specific CB1 receptor antagonist, SR 141716A, dissolved in an aqueous 42% 2-HP-β-CD solution. AEA, its R-alpha-isopropyl analog, and CP-55,940 reduced IOP upon topical application to a greater degree than was detected in the untreated eye. This reduction was eliminated for the latter two compounds by subcutaneous (s.c.) pretreatment of the rabbits with the CB1 receptor antagonist, but the IOP properties of AEA remained unchanged. SR 141716A administered alone (s.c.), elevated the IOP of both eyes. A CB1 receptor seems involved in the IOP reduction induced by either R-alpha-isopropyl anandamide or CP-55,940. However, AEA apparently functions through a different mechanism.

References (14)

  • Y. Mikawa et al.

    Jpn. J. Opthalmol.

    (1997)
  • D.W. Pate et al.

    Life Sci.

    (1996)
  • M. Rinaldi-Carmona et al.

    FEBS Lett.

    (1994)
  • S. Matsuda et al.

    Exp. Eye Res.

    (1997)
  • L. Salminen et al.

    Exp. Eye Res.

    (1984)
  • R.S. Hepler et al.

    J. Am. Med. Assn.

    (1971)
  • B.K. Colasanti

    J. Ocular Pharmacol.

    (1986)
There are more references available in the full text version of this article.

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This work was supported by grants from the Academy of Finland and the Technology Development Center (Finland).

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