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Abstract #14718 Published in IGR 8-4
Ocular hypotensive effects of an intratracheally delivered liposomal Δ9-tetrahydrocannabinol preparation in rats
Szczesniak A-M; Kelly MEM; Whynot S; Shek PN; Hung OJournal of Ocular Pharmacology and Therapeutics 2006; 22: 160-167
This study investigated the effect of an intrairacheal (i.t.) administration of a liposome-entrapped Δ9-tetrahydrocannabinol (LTHC) preparation on intraocular pressure (IOP) in nonanaesthetized Brown Norway rats. The ocular hypotensive effects of i.t. LTHC were compared to that of intraperitoneal (i.p.) LTHC administration. All i.t. LTHC doses > 0.05 mg/kg significantly decreased IOP (P < 0.05) within 30 min of administration, and doses of i.t. LTHC > 0.1 mg/kg decreased IOP within 15 min of administration. A maximal reduction in IOP of 2.32 ± 0.27 mmHg (n = 4) was seen with 1.0 mg/kg of i.t. LTHC. In comparison, no significant IOP drop was apparent prior to 30 min with all doses (0.01-1.0 mg/kg) of i.p. LTHC tested, although a similar maximum drop in IOP (2.15 ± 0.12 mmHg; n = 8) was obtained with 1.0 mg/kg of LTHC. The ED50 for i.t. and i.p. LTHC was 0.08 mg/kg and 0.12 mg/kg, respectively. The IOP-lowering effects of i.p. LTHC (0.2 mg/kg) were reduced by 14% and 80% by 0.25 mg/kg (n = 6) arid 2.5 mg/kg (n = 6), respectively, of the CB1R antagonist, SR141716A. In conclusion, i.t. LTHC was superior to i.p. LTHC in producing a more rapid and potent decrease in IOP. The IOP-lowering effect of LTHC was blocked by the CB1R-selective antagonist, SR141716A, suggesting that CB1Rs contribute to the ocular hypotensive effect of Δ9-tetrahydrocannabinol.
Dr. O. Hung, Department of Anaesthesia, Queen Elizabeth II Health Science Centre, 1278 Tower Road, Halifax, NS B3H 2Y9, Canada
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5 Experimental glaucoma; animal models
