The ocular hypotensive action of SK&F 86466 in the conscious rabbit

SK&F 86466, 6-chloro-3-methyl-2,3,4,5-tetra-hydro-1H-3-benzazeplne, a potent and selective competitive antagonist of the alpha2-adrenoceptor is of interest as a potential antlglaucoma agent. Following instillation into the rabbit eye, SK&F 86466 produced concentration (0.25 to 10%) dependent reductions in intraocular pressure (IOP). The ocular hypotensive effect of SK&F 86466 was maximal 30-60 minutes post treatment and persisted for at least 90 minutes. The IOP of the contralateral (untreated) eye was significantly decreased only at the 10% concentration. A 10% solution of SK&F 86466 had no significant effect on mean arterial blood pressure (MAP) of rabbits during the time of maximal bilateral ocular hypotensive activity. These results suggest: (1) a selective alpha2-adrenoceptor antagonist can reduce IOP when applied topically to rabbit eyes and (2) the ocular hypotensive effect of SK&F 86466 Is not secondary to a reduction In systemic blood pressure.