Ocular effects of dipivalyl esters of epinephrine and α-methylepinephrine

Abstract

The intraocular pressure (IOP) and pupillary effects of dipivalyl esters of epinephrine and α-methylepinephrine were compared after topical application in conscious rabbits. Both dipivalyl-α-methylepinephrine (DPαmeE) and dipivalylepinephrine (DPE) produced a dose-dependent pupillary dilation (PD) and decrease in IOP. The onset of PD was approximately 30 min for both agents and reached maximal plateau within 1 and 2 hr for DPE and DPαmeE, respectively. Duration of mydriatic effect was also dose-related, although more prolonged with DPαmeE. This probably reflects differences in rate of inactivation of these compounds. The onset of IOP lowering effect of DPαmeE was more rapid (35–45 min) when compared with DPE (1·5-2 hr) which may be due to the initial ocular hypertensive response seen with DPE. The initial rise in IOP was prevented by transection of three rectus muscles. DPαmeE produced initial ocular hypertension only at the highest doses. The decrease of IOP lasted more than 6 hr for both drugs, returning to normal by 24 hr. No pupillary or IOP effects were seen in the contralateral eye. Denervation supersensitivity to both the pupillary and IOP responses to DPαmeE was seen after superior cervical ganglionectomy. These findings are consistent with the hypothesis that the pupillary and IOP responses to DPαmeE do not require intact adrenergic innervation to the eye, and that these effects are mediated by activation of postjunctional α-adrenoceptors. It is concluded that DPαmeE is a potent adrenergic ocular hypotensive agent. In comparison to DPE, DPαmeE has a more rapid onset, longer duration of action, less pupillary effect, and produces ocular hypotension with less initial ocular hypertension.