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M.H. Oltmanns, S.S. Samudre, F.A. Lattanzio, Jr., R.C. Allen, B.R. Martin, I.G. Castillo; Comparison of Systemic and IOP Effects With Intravenous or Topical WIN 55–212–2 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):401.
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© ARVO (1962-2015); The Authors (2016-present)
Systemic administration of cannabinoids decreases IOP, but with unwanted side effects. Topical application may provide an equivalent effect on IOP but with fewer or no adverse effects, e.g altered heart rate (HR) or blood pressure (BP). This study compared topical with IV administration of synthetic WIN 55, 212–2 and endogenous anandamide.
Topical WIN–55–212–2 (0.125% – 1.0% w/v) dissolved in Tocrisolve and IV WIN–55–212–2 (0.01 – 0.1 mg/kg) and anandamide (0.01 – 0.1 mg/kg) dissolved in ethanol, Emulphor and saline (1:1:4) were administered to New Zealand white rabbits. IOP (mm Hg), BP (mm Hg) and HR (bpm) were measured from 30 – 120 min. IOP was recorded using pneumotonometry (Mentor, Norwell, MA) and BP and HR using a tail cuff apparatus was analyzed with DasyLab (DasyTEC, Amherst, NH).
Following IV administration, WIN 55–212–2 (0.01 mg/kg) reduced IOP by 24.5±5.0% and 0.1 mg/kg by 33.0±12.4% (p= 0.05). Although anandamide (0.01 mg/kg) decreased IOP by 29.4±8.8%, 0.1 mg/kg caused no additional effect as IOP decreased by 21.1±6.8% (p=0.482). At 0.01 mg/kg neither Win–55–212–2 nor anandamide affected BP, but both significantly decreased HR; Win–55–212–2 decreased HR from 233±15 to 197±6 and anandamide from 260±25 to 239±9. At 0.1 mg/kg both drugs significantly decreased BP and HR. Win 55–212–2 decreased systolic BP from 105±10 to 85±2 and diastolic BP from 65±9 to 44±5. Anandamide decreased systolic BP from 83±6 to 73±2 and diastolic BP from 49±3 to 39±3. In comparison, after topical administration, 1.0% WIN–55–212–2 reduced IOP from baseline (20.5±3.5 mmHg) to 17.2±2.7 mmHg (16% decrease) at 30 min (p=0.003). Similarly 0.5% WIN 55–212–2 reduced IOP by 10% at 30 min (p=0.014). Lower concentrations had no effect. No change in BP or HR was noted after topical treatment (p= 0.960). In addition, topical administration had no toxic effects on ocular tissues.
Although with IV administration effects on IOP were pronounced, adverse systemic effects and inconsistent response preclude their use. While not as efficacious, topical administration is the safer alternative due to the more consistent effect on IOP and concomitant lack of toxic systemic or local toxicity.
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