The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist.

PURPOSE AND METHODS: The aim of this study was to determine the ocular pharmacological characteristics of AL-34662 (1-((S)-2-aminopropyl)-1H-indazole-6-ol), a new synthetic serotonin-2 (5-HT2) receptor-agonist ocular hypotensive agent. A variety of well-documented in vitro and in vivo procedures were utilized to study the pharmacological attributes of AL-34662. RESULTS: AL-34662 exhibited a high affinity for the rat and human 5-HT2 receptor (IC50=0.8-1.5 nM) and for cloned human 5-HT2A-C receptors (IC50=3-14.5 nM). AL-34662 stimulated phosphoinositide turnover in human ciliary muscle (h-CM; EC50=289+/-80 nM) and in human trabecular meshwork (h-TM; EC50=254+/-50 nM) cells. AL-34662 also mobilized intracellular Ca2+ ([Ca2+]i) in h-CM (EC50=140+/-23 nM) and h-TM (EC50=38+/-8 nM) cells, being a full agonist like 5-HT itself. AL-34662's effects in the h-CM (and h-TM) cells were potently antagonized by 5-HT2A-antagonist M-100907 (IC50=1.8+/-0.7 nM), but weakly by 5-HT2B-antagonist (RS-127445 IC50>10 microM), 5-HT2B/C- antagonist (SB-242084 IC50=2.08 microM) and 5-HT2C antagonist (RS-102221 IC50>1 microM). AL-34662 caused relatively minimal ocular discomfort and hyperemia in rabbit and guinea pig eyes. It efficaciously lowered intraocular pressure (IOP) in the conscious ocular hypertensive monkey eyes (33% at 300 microg). The (R)-enantiomer (AL-34707) and the racemate (AL-34497) were less potent and/or efficacious than AL-34662 in all of these assays. CONCLUSIONS: AL-34662 is a high-affinity 5-HT2 receptor agonist that potently mobilizes [Ca2+]i in h-CM and h-TM cells, and which efficaciously lowers IOP in conscious ocular hypertensive cynomolgus monkey eyes through a local effect with minimal side-effects.[1]


  1. AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist. Sharif, N.A., McLaughlin, M.A., Kelly, C.R. J. Ocul. Pharmacol. Ther (2007) [Pubmed]
WikiGenes - Universities