Evaluation of IBMX-enhanced ocular hypotension after adrenergic agonists in the rabbit eye.
BACKGROUND
3-Isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, enhanced the reduction of intraocular pressure more after administration of norepinephrine and epinephrine than after isoproterenol. The question arises of whether or not the IBMX-induced enhancement of ocular hypotension is exclusively due to beta 2-adrenoceptor/cAMP stimulation.


METHODS
In groups of eight rabbits the ocular hypotensive responses after selective adrenergic agonists were studied in the presence and absence of phosphodiesterase inhibition with IB-MX.


RESULTS
Pretreatment with IBMX 1%, applied topically, did not enhance the ocular hypotensive responses after phenylephrine (alpha 1), B-HT920 (alpha 2) and dobutamine (beta 1). The ocular hypotensive responses induced by salbutamol (0.001-0.5%) and higher concentrations of terbutaline were significantly enhanced by IBMX. Combined treatments of terbutaline 0.01% and B-HT920 0.2%, dobutamine 3% and phenylephrine 2%, and dobutamine 3% and B-HT920 0.2% were not associated with enhanced ocular hypotensive responses in the presence of IBMX. The only combination that 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 enhanced ocular hypotensive responses induced by salbutamol 0.025, 0.2 and 0.5% in combination with IBMX.


CONCLUSIONS
Phosphodiesterase inhibition with IB-MX enhances the ocular hypotensive effect induced by catecholamines not only by beta 2-adrenoceptor/cAMP stimulation, but also by simultaneous alpha 1-adrenoceptor stimulation.
Busch
M J
MJ
Department of Experimental Ophthalmology, The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands.
Hoyng
P F
PF
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000494:pharmacology*; D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D015814:Ocular Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D009883:Ophthalmic Solutions; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D015056:1-Methyl-3-isobutylxanthine