{'fraction_non_alphanumeric': 0.05449398443029016, 'fraction_numerical': 0.06510969568294409, 'mean_word_length': 4.48062015503876, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Novel Endocannabinoids Reduce Intraocular Pressure in a Rat Glaucoma Model

Naturally occurring cannabinoids, like Δ9‐THC, decrease intraocular pressure (IOP), but significant systemic effects preclude their use to treat glaucoma. Synthetic cannabinoids, e.g. WIN 55‐212‐2, a CB1,2 agonist, are more potent and more water soluble. Topical ocular effects of newly synthesized CB agonists, lipid soluble O‐1812 (CB1,2), water soluble O‐2545 (CB1,2) and O‐2365 (CB1 > CB2) on IOP, heart rate (HR) and blood pressure (BP) were examined in a surgical rat glaucoma model. Baseline IOP was 14.1 ± 0.6 mm Hg, BP = 134 ± 8/98 ± 8 mm Hg; and HR = 349 ± 30BPM. All drugs showed maximal IOP decrease at 60 min and returned to normal by 120 min, except for 0.1% O‐1812, whose maximal effect was at 30 min and 1.0 % O‐2545, which sustained the IOP drop for 120 min. Neither the vehicle alone nor the inactive enantiomer, WIN 55‐212‐3, had an effect on IOP. No significant effects on HR and BP wereobserved. No ocular irritation was observed by slit lamp examination. All 4 CB agonists effectively decreased IOP without systemic effects. All 3 novel agents were equipotent. Lipid soluble O‐1812 had the most rapid onset, but the more water soluble O‐2545 had the longest duration of action. Based upon their potency in the CNS, the 3 agents were expected to be 2‐10 X more potent than Win 55‐212‐2, but none were as efficacious.