EVALUATION OF IBMX-ENHANCED OCULAR HYPOTENSION AFTER ADRENERGIC AGONISTS IN THE RABBIT EYE

Background: 3-Isobutyl-1-methylxanthine (IBMX), a phosphodiesterase in hibitor, enhanced the reduction of intraocular pressure more after adm inistration of norepinephrine and epinephrine than after isoproterenol . The question arises of whether or not the IBMX-induced enhancement o f ocular hypotension is exclusively due to beta(2)-adrenoceptor/cAMP s timulation. Methods: In groups of eight rabbits the ocular hypotensive responses after selective adrenergic agonists were studied in the pre sence and absence of phosphodiesterase inhibition with IBMX. Results: Pretreatment with IBMX 1%, applied topically, did not enhance the ocul ar hypotensive responses after phenylephrine (alpha(1)), B-HT920 (alph a(2)) and dobutamine (beta(1)). The ocular hypotensive responses induc ed by salbutamol (0.001-0.5%) and higher concentrations of terbutaline were significantly enhanced by IBMX. Combined treatments of terbutali ne 0.01% and B-HT920 0.2%, dobutamine 3% and phenylephrine 2%, and dob utamine 3% and B-HT920 0.2% were not associated with enhanced ocular h ypotensive responses in the presence of IBMX. The only combination tha t was associated with a significant enhancement of ocular hypotension when combined with 1% IBMX was phenylephrine 2% and terbutaline 0.01%. A subthreshold dose of phenylephrine 0.1% further increased the enhan ced ocular hypotensive responses induced by salbutamol 0.025, 0.2 and 0.5% in combination with IBMX. Conclusions: Phosphodiesterase inhibiti on with IBMX enhances the ocular hypotensive effect induced by catecho lamines not only by beta(2)-adrenoceptor/cAMP stimulation, but also by simultaneous alpha(1)-adrenoceptor stimulation.