The influence of topically applied selective alpha 1-and alpha 2-adrenoceptor agonists on intraocular pressure and the diameter of the pupil was investigated in conscious rabbits. Selective stimulation of the alpha 1-subtype of receptors induced an elevation in intraocular pressure, accompanied by mydriasis, whereas stimulation of the alpha 2-subtype caused a marked and dose-dependent ocular hypotensive response, which was blocked by the selective alpha 2-adrenoceptor antagonist yohimbine. alpha 2-Agonists induced neither macroscopic ocular side effects, nor an effect on the pupil size. Possibly, the subclass of alpha 2-adrenoceptor stimulating drugs represents a group of new antiglaucomatous agents.

No abstract

Clonidine was administered into the left vertebral artery of anesthetized cats. A dose-response curve of the lowering effect on intraocular pressure (IOP) has been made and compared with the dose-response cure obtained after intravenous administration. A more pronounced decrease in IOP after the first route of administration became evident. The effect is not secondary to a stronger reduction of blood pressure by centrally injected clonidine. Distribution experiments with 14C-clonidine revealed no direct connection between the vertebral arteries and the blood supply of the eye. For 2 h the concentrations in the eye are somewhat lower than after intravenous administration. Therefore, the IOP-lowering effect is not due to a direct influence of clonidine on the eye. It is submitted that the clonidine-induced reduction in IOP is at least in part due to a central mechanism, in which the stimulation of central alpha-adrenoceptors and adrenergic neurons may be involved. The relevance of this hypothesis with regard to a possible central regulation of IOP is discussed.

Clonidine was topically applied to the right eye of anesthetized cats. Unilateral administration induced a fall in intraocular pressure (IOP) in both eyes. This effect is not secondary to the slight fall in arterial blood pressure. Distribution experiments with 14C-clonidine revealed that only minor or negligible amounts of clonidine could be demonstrated in the contralateral eye. The concentrations of the labeled drug determined in the brain after topical application are sufficient to explain the bilateral decrease in IOP by a central mechanism. The IOP-lowering effect of clonidine upon its topical application to the eye is probably of central nervous origin and, therefore, similar to the centrally induced effect on IOP after systemic administration of the drug.

A comparison was made between the ocular penetration of topically applied 14C-atenolol, 14C-timolol, 14C-propranolol and 3H-metoprolol by means of liquid scintillation counting. Only one eye was treated, the fellow eye served as a control. Blood plasma levels were measured as well. We could detect a relationship between the ocular penetration and the degree of lipophilicity of the drugs used, as was to be expected. Drugs with a higher degree of lipophilicity penetrated more readily into the eye, whereas they also achieved higher blood plasma levels. Relatively high concentrations of atenolol were found in the nicitating membrane, thus reflecting its poor ocular penetration. The concentrations detected in the untreated eye were low and probably cannot explain the marked reduction in intraocular pressure observed after unilateral instillation of active beta-adrenergic blocking drugs, as for instance timolol. Our findings suggest that the ocular penetration of beta-adrenergic blocking agents on topical application only plays a minor part in their ocular hypotensive effect.