Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid
Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid
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DOI：
10.1089/jop.2000.16.217
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发表时间：
2000-06-01
影响因子：
2.3
通讯作者：
Bar-Ilan, A
中科院分区：
文献类型：
--
作者：
Beilin, M;Neumann, R;Bar-Ilan, A
本研究的目的是观察合成非精神药物大麻素地脚大麻酚（HU-211） [(+)(3S,4S)， 7-羟基- δ -6-四氢大麻酚1,1二甲基庚基]在家兔静脉（i.v）给药后降低眼压（IOP）的活性及其可能的作用机制。在未麻醉的白化兔中测量IOP（气压计）、房水流入率（荧光光度计）、血压和心率（连接中央耳动脉插管的计算机生理测量系统）。静脉给药HU-211导致IOP的剂量相关性降低；在0.5 mg/kg剂量后4小时观察到最大IOP降低5.0 +/- 0.2 mmHg。在该剂量HU-211后的第一个小时内，血压或心率没有明显变化。在0.5 mg/kg静脉注射后的5小时内，瞳孔直径没有明显变化。在0.5 mg/kg剂量的HU-211后的6小时内房水流入速率没有发生显著变化，从而暗示流出量的变化是IOP降低的主要来源。在α(2)肾上腺素能拮抗剂育喜宾（1mg /kg，静脉注射）预处理后，HU-211的眼压降低率仅为单独使用HU-211的30%。用α(2)激动剂可乐定（0.5 mg/kg静脉注射）预处理后的IOP降低是单独使用HU-211的两倍。用β -肾上腺素能拮抗剂普萘洛尔（0.5 mg/kg静脉注射）预处理，可使HU-211的降眼压作用降低50%。总之，HU-211静脉注射是一种有效的降低内压的药物，没有任何明显的副作用（血压、心率或瞳孔直径，所有这些都是以前大麻素的报道）。肾上腺素能系统参与调节HU-211降低眼压的作用，这似乎反映了眼内液体流出的变化。
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 4 hr after a 0.5 mg/kg dose. No significant changes in blood pressure or heart rate were observed during the first hr following this dose of HU-211. Pupil diameter did not change significantly during the 5 hr following the 0.5 mg/kg i.v. dose. No significant change in the rate of aqueous humor inflow occurred during the 6 hr 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 alpha(2) adrenergic antagonist, yohimbine (1 mg/kg, i.v.), was only 30% of that of HU-211 alone. IOP reduction following pretreatment with the alpha(2) 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.