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Pharmacological Profile of the Selective FAAH Inhibitor KDS‐4103 (URB597)
Get PDFIn the present article, we review the pharmacological properties of KDS-4103 (URB597), a highly potent and selective inhibitor of the enzyme fatty-acid amide hydrolase (FAAH), which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide. In vitro, KDS-4103 inhibits FAAH activity with median inhibitory concentrations (IC(50)) of 5 nM in rat brain membranes and 3 nM in human liver microsomes. In vivo, KDS-4103 inhibits rat brain FAAH activity after intraperitoneal (i.p.) administration with a median inhibitory dose (ID(50)) of 0.15 mg/kg. The compound does not significantly interact with other cannabinoid-related targets, including cannabinoid receptors and anandamide transport, or with a broad panel of receptors, ion channels, transporters and enzymes. By i.p. administration to rats and mice KDS-4103 elicits significant, anxiolytic-like, antidepressant-like and analgesic effects, which are prevented by treatment with CB1 receptor antagonists. By contrast, at doses that significantly inhibit FAAH activity and substantially raise brain anandamide levels, KDS-4103 does not evoke classical cannabinoid-like effects (e.g., catalepsy, hypothermia, hyperphagia), does not cause place preference, and does not produce generalization to the discriminative effects of the active ingredient of cannabis, Delta9-tetrahydrocannabinol (Delta9-THC). These findings suggest that KDS-4103 acts by enhancing the tonic actions of anandamide on a subset of CB(1) receptors, which may normally be engaged in controlling emotions and pain. KDS-4103 is orally available in rats and cynomolgus monkeys. Sub-chronic repeated dose studies (1,500 mg/kg, per os) in these two species have not demonstrated systemic toxicity. Likewise, no toxicity was noted in bacterial cytotoxicity tests in vitro and in the Ames test. Furthermore, no deficits were observed in rats on the rotarod test after acute i.p. treatment with KDS-4103 at doses up to 5 mg/kg or in a functional observation battery after oral doses up to 1,500 mg/kg. The results suggest that KDS-4103 will offer a novel approach with a favorable therapeutic window for the treatment of anxiety, depression and pain
St. Louis & San Francisco (SLSF) "Frisco" 4103
No full textA photograph postcard showing the St. Louis & San Francisco (SLSF) "Frisco" 4103, 2-8-2, on southbound freight approaching Ada, OK, 51 cars, 30 mph
Block Card 4103 Commonwealth Avenue
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: dwelling | 4103 Commonwealth Avenue (Toledo, Ohio) | Side gabled | Craftsman Style | Commonwealth Addition (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | Folk House Styl
Block Card 4103 Walker Avenue
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4103 Walker Avenue (Toledo, Ohio) | Willys Park Area (Toledo, Ohio) | West Toledo Area (Toledo, Ohio) | Gable front houses | Folk House Styl
Block Card 4103 Ruskin Drive
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | Dwelling | Fuller's Mount Vernon Addition (Toledo, Ohio) | Inverness Area (Toledo, Ohio) | 4103 Ruskin Drive (Toledo, Ohio
Chicago, Burlington & Quincy (CBQ) 4103
No full textA photograph print showing Chicago, Burlington & Quincy (CBQ) 4103, 2-6-6-2, (BLW Class T-2), compound. Locomotives of this type were used in the Black Hills as pushers (note that this photo has been printed backwards). [Owen Goerke, Gillettte, WY?
Block Card 4103 Amsterdam Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | Dwelling | Fuller's Mount Vernon Addition (Toledo, Ohio) | Inverness Area (Toledo, Ohio) | 4103 Amsterdam Road (Toledo, Ohio
Linked collectors and determiners for: Contributions to the knowledge of Umbrageocoris (Heteroptera: Lygaeoidea: Geocoridae).
No full textNatural history specimen data linked to collectors and determiners held within, "Contributions to the knowledge of Umbrageocoris (Heteroptera: Lygaeoidea: Geocoridae)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/e7eb57ba-824d-4103-87fd-9a69777bae62">https://bionomia.net/dataset/e7eb57ba-824d-4103-87fd-9a69777bae62</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/e7eb57ba-824d-4103-87fd-9a69777bae62">https://gbif.org/dataset/e7eb57ba-824d-4103-87fd-9a69777bae62</a>. Formatted as a Frictionless Data package
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