caa a22 4500 477126561 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012131929940 doi (NATIONALLICENCE)springer-10.1023/A:1012131929940 Effects of Topical alpha-Substituted Anandamides on Intraocular Pressure in Normotensive Rabbits [Elektronische Daten] [David Pate, Kristiina Järvinen, Arto Urtti, Pekka Jarho, Vaidyanath Mahadevan, Tomi Järvinen] Purpose. Anandamides have been observed to lower intraocular pressure in the rabbit eye, preceded by a period of hypertension. Amidases are thought to catabolize these compounds into their component parts, including arachidonic acid. Direct application of arachidonic acid has been observed to cause a marked rise of intraocular pressure. Thus, anandamide analogs resistant to catabolism were thought possibly devoid of this initial hypertension, and their effects on rabbit IOP investigated. Methods. A series of chiral alpha-substituted anandamides were synthesized and studied for their effect on the intraocular pressure (IOP) of normotensive pigmented rabbits. Each test compound was dissolved in an aqueous 2-hydroxypropyl-β-cyclodextrin solution (containing 3% polyvinyl alcohol) and administered (62.5 μg) unilaterally to the eye. Results. The most promising compounds caused a statistically significant reduction of IOP (vs. vehicle) in the treated eyes. Of these, the R-alpha-isopropyl compound exhibited the best activity tested. Unlike the alpha-unsubstituted analogs previously studied, hypotensive effects were not preceded by an initial elevation of IOP and indomethacin pre-treatment (12.5 mg, s.c.) did not eliminate the IOP response, as demonstrated by administered R-alpha-isopropyl anandamide. Conclusions. Catabolism of alpha-unsubstituted anandamides may account for their observed intraocular hypertensive effects. The physiological mechanism by which alpha-substituted anandamides work apparently differs from that of the more easily metabolized alpha-unsubstituted compounds. Plenum Publishing Corporation, 1997 anandamides nationallicence intraocular pressure nationallicence cyclodextrin nationallicence indomethacin nationallicence rabbit nationallicence Pate David Department of Pharmaceutical Chemistry, University of Kuopio, Finland aut Järvinen Kristiina Department of Pharmaceutics, University of Kuopio, Finland aut Urtti Arto Department of Pharmaceutics, University of Kuopio, Finland aut Jarho Pekka Department of Pharmaceutical Chemistry, University of Kuopio, Finland aut Mahadevan Vaidyanath Deva Biotech, Inc., Hatboro, Pennsylvania, USA aut Järvinen Tomi Department of Pharmaceutical Chemistry, University of Kuopio, Finland aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1738-1743 0724-8741 14:12<1738 1997 14 11095 https://doi.org/10.1023/A:1012131929940 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012131929940 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pate David Department of Pharmaceutical Chemistry, University of Kuopio, Finland aut NATIONALLICENCE 700 1- Järvinen Kristiina Department of Pharmaceutics, University of Kuopio, Finland aut NATIONALLICENCE 700 1- Urtti Arto Department of Pharmaceutics, University of Kuopio, Finland aut NATIONALLICENCE 700 1- Jarho Pekka Department of Pharmaceutical Chemistry, University of Kuopio, Finland aut NATIONALLICENCE 700 1- Mahadevan Vaidyanath Deva Biotech, Inc., Hatboro, Pennsylvania, USA aut NATIONALLICENCE 700 1- Järvinen Tomi Department of Pharmaceutical Chemistry, University of Kuopio, Finland aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1738-1743 0724-8741 14:12<1738 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer