Comparison of Topical and Intravenous Administration of WIN 55-212-2 in Normotensive Rabbits

Abstract

Topical administration of either WIN or timolol did not decrease IOP as much as IV administration, but the lack of systemic or local toxicity could make it the safer alternative.

TheIn VivoEffects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice

“…The GAT229-induced increase in the duration of the IOP-lowering effect is in contrast to the relatively shortlived actions of acute orthosteric CB 1 activation by can-nabinoids, typically lasting only about 1-2 h after administration. [12][13][14]16,28,65,66 We found that whereas administration of 1% WIN alone reduced IOP for *1 h, the combination of subthreshold (0.25%) WIN with GAT229 reduced IOP for at least 6 h in normotensive mice. Duration of action is important when considering use as a clinically relevant therapeutic; drugs with short durations of action require frequent administration, which may lead to issues with patient compliance.…”

“…4,5 Activation of cannabinoid receptor 1 (CB 1 ), through topical, oral, and inhaled routes of administration of synthetic cannabinoids and phytocannabinoids, decreases IOP in both animal models and humans. [7][8][9][10][11][12][13][14][15][16][17][18][19] The mechanism of these hypotensive effects involves local actions that may affect both aqueous humor inflow and outflow, [20][21][22][23][24][25][26][27] and also appears to involve, at least in part, b adrenergic receptors. 28 Although glaucomatous RGC death has been extensively studied, [29][30][31][32][33][34] to date, no drug designed specifically as an RGC neuroprotectant has successfully made it to the market.…”