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Abstract #15920 Published in IGR 2-3
Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid
Beilin M; Neumann R; Belkin M; Green K; Bar-Ilan AJournal of Ocular Pharmacology and Therapeutics 2000; 16: 217-230
The purpose of this study was to characterize the intraocular pressure (IOP) lowering activity and possible mechanism of action of the synthetic, non-psychotropic cannabinoid dexanabinol (HU-211) ((+) (3S,4S), 7-hydroxy-delta-6-tetrahydrocannabinol 1,1 dimethylheptyl), following intravenous (i.v.) administration in the rabbit. IOP (pneumatonometry), aqueous humor inflow rate (fluorophotometry), blood pressure, and heart rate (computerized physiograph system connected to central ear artery cannula) were measured in unanesthetized albino rabbits. Intravenous administration of HU-211 resulted in a dose-related reduction in IOP; a maximal IOP reduction of 5.0 ± 0.2 mmHg was observed four hours after a 0.5 mg/kg dose. No significant changes in blood pressure or heart rate were observed during the first hour following this dose of HU-21 1. Pupil diameter did not change significantly during the five hours following the 0.5 mg/kg i.v. dose. No significant change in the rate of aqueous humor inflow occurred during the six hours after a 0.5 mg/kg dose of HU-211, thereby implicating outflow changes as the major source of IOP reduction. IOP reduction by HU-211 following pre-treatment with the α2 adrenergic antagonist, yohimbine (1 mg/kg, i.v.), was only 30% of that of HU-211 alone. IOP reduction following pretreatment with the α2 agonist, clonidine (0.5 mg/kg i.v.), was twice as large as that of HU-211 alone. Pretreatment with the beta-adrenergic antagonist, propranolol (0.5 mg/kg i.v.), resulted in a 50% reduction in the IOP-lowering effect of HU-211. In summary, HU-211, administered i.v., is an effective IOP-lowering agent, devoid of any significant side effects (blood pressure, heart rate or pupil diameter, all of which have been reported previously for cannabinoids). Involvement of the adrenergic system is indicated in mediating the IOP-lowering effects of HU-211 that appear to reflect a change in fluid outflow from the eye.
Dr. M. Beilin, Pharmos Corporation, Ltd., Kiryat Weizmann, Rehovot, Israel
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)