Isobutylmethylxanthine enhances adrenergic-induced ocular hypotension in rabbits and beagles.
Isobutylmethylxanthine (IBMX), a phosphodiesterase/adenosine receptor inhibitor, was combined with norepinephrine (nE), epinephrine (Epi) and isoproterenol, respectively, to evaluate their effect on intraocular pressure (IOP). Application of topical IBMX alone had no measurable effect on IOP. When IBMX was combined with nE or Epi the ocular hypotension in rabbits and beagles increased. The Emax for nE alone was 2.9 +/- 0.4 mmHg, for Epi alone 7.3 +/- 0.5 mmHg and for isoproterenol alone 5.1 +/- 0.3 mmHg. The EC50 was 0.2 +/- 0.05% (nE), 0.05 +/- 0.01% (Epi) and 0.003 +/- 0.001% for isoproterenol. When given in combination with 1% IBMX the Emax for nE was 7.4 +/- 1.7 mmHg, for Epi 9.0 +/- 0.8 mmHg and for isoproterenol 6.1 +/- 0.3 mmHg. The corresponding values for EC50 were 0.07 +/- 0.03% (nE), 0.02 +/- 0.006% (Epi) and 0.002 +/- 0.001% for isoproterenol. Combining 1% IBMX with 0.1% Epi increased the aqueous humour cyclic AMP-levels at 1, 3 and 5 hr in rabbits. The results of this study demonstrate that a phosphodiesterase/adenosine receptor inhibitor such as IBMX enhances the reduction in IOP induced by adrenergic agonists.
Hoyng
P F
PF
The Netherlands Ophthalmic Research Institute, Department of Experimental Ophthalmology, Amsterdam-ZO.
Groeneboer
M C
MC
Busch
M J
MJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D005136:Eye Proteins; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine; D004837:Epinephrine