Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 12479982

Topically administered CB(2)-receptor agonist, JWH-133, does not decrease intraocular pressure (IOP) in normotensive rabbits.

Krista Laine·Kristiina Järvinen·Tomi Järvinen
View original source ↗Export metadata ↓

Abstract

Recent IOP and receptor localization studies suggest that the IOP effects of cannabinoids are mediated via ocular CB(1) receptors. However, it is not yet known whether CB(2) receptor agonists decrease IOP. In this study, the IOP-lowering effects of the CB(2) receptor agonist JWH-133 were studied in normotensive rabbits, and compared with CP55,940. JWH-133 and CP55,940 were dissolved in aqueous hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solutions and propylene glycol. The eye drops (25 microl) were administered unilaterally to the rabbit eye, and IOPs were measured at fixed time intervals. JWH-133, dissolved in either HP-beta-CD (doses = 10 microg and 25 microg) or propylene glycol (dose = 62.5 microg), did not have any effect on IOP when compared to vehicle treatments. In contrast, CP55,940 formulated in HP-beta-CD (doses = 25 microg and 62.5 microg) or propylene glycol (dose = 62.5 microg) reduced IOP significantly compared to vehicle treatments. The results suggest that topically administered CB(2) receptor agonist, JWH-133, does not decrease IOP in normotensive rabbits at the doses and formulations used, and thus, CB(2) receptor agonists may not be useful as cannabinoid-based IOP-lowering therapeutics.

Explore related subjects

Administration, TopicalAnimalsAntineoplastic AgentsCannabinoidsCyclohexanolsDose-Response Relationship, DrugFemaleIntraocular PressureMaleRabbitsReceptors, CannabinoidReceptors, DrugComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Krista Laine, Kristiina Järvinen, Tomi Järvinen. 2003-01-03. Topically administered CB(2)-receptor agonist, JWH-133, does not decrease intraocular pressure (IOP) in normotensive rabbits.. https://doi.org/10.1016/s0024-3205(02)02339-1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2003

Poly(butylcyanoacrylate) nanoparticles for topical delivery of 5-fluorouracil.

Poly(butylcyanoacrylate) nanoparticles (PBCN) as a drug carrier of 5-fluorouracil (5FU) intended for topical treatment of skin lesia were investigated. The presence of 5FU (as saline solution, pH 10-11) in the polymerization medium affected the polymerization as well as the nanoparticle formation by influencing the initiation of the polymerization reaction. 5FU acted as an initiator in the anionic polymerization of n-butylcyanoacrylate monomer through its nucleophilic nitrogen centers. The results obtained by GPC, 1H NMR, and X-ray diffraction allude to a possible mechanism of cytostatic immobilization in the polymer matrix, with evidence for both free and bound forms of the drug.

Administration, Topical↗
PubMed2003

A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indole.

Serotonin 5-HT2 receptor agonists have recently been shown to be effective in lowering intraocular pressure in nonhuman primates and represent a potential new class of antiglaucoma agents. As part of an effort to identify new selective agonists at this receptor, we have found that (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indole (AL-37350A, 11) has high affinity and selectivity (>1000-fold) for the 5-HT(2) receptor relative to other 5-HT receptors. More specifically, 11 is a potent agonist at the 5-HT2A receptor (EC50 = 28.6 nM, E(max) = 103%) that is comparable to serotonin. Evaluation of 11 in conscious ocular hypertensive cynomolgus monkeys showed this compound to be efficacious in reducing intraocular pressure (13.1 mmHg, -37%). Thus, 11 is a potent full agonist with selectivity for the 5-HT2 receptor and is anticipated to serve as a useful tool in exploring the role of the 5-HT2 receptor and its effector system in controlling intraocular pressure.

Administration, Topical↗