PubMed · 9529509
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G D Murray. 1998. Statistical commentary.. https://pubmed.ncbi.nlm.nih.gov/9529509/
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The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA). CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete Freund's adjuvant. The CII used was either bovine or murine, resulting in classical acute CIA or in chronic relapsing CIA, respectively. CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked progression of arthritis. CBD was equally effective when administered i.p. or orally. The dose dependency showed a bell-shaped curve, with an optimal effect at 5 mg/kg per day i.p. or 25 mg/kg per day orally. Clinical improvement was associated with protection of the joints against severe damage. Ex vivo, draining lymph node cells from CBD-treated mice showed a diminished CII-specific proliferation and IFN-gamma production, as well as a decreased release of tumor necrosis factor by knee synovial cells. In vitro effects of CBD included a dose-dependent suppression of lymphocyte proliferation, both mitogen-stimulated and antigen-specific, and the blockade of the Zymosan-triggered reactive oxygen burst by peritoneal granulocytes. It also was found that CBD administration was capable of blocking the lipopolysaccharide-induced rise in serum tumor necrosis factor in C57/BL mice. Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect in CIA.
The new chemical entity CGP 70726, a very poorly water-soluble HIV-1 protease inhibitor, was incorporated into pH-sensitive nanoparticles and microparticles made of the poly(methacrylic acid-co-ethylacrylate) copolymer Eudragit((R)) L100-55. The particles were characterized in terms of morphology, size distribution, drug loading, production yield and dispersion state of the drug inside the polymeric matrices. Aqueous dispersions of the particles were administered orally to Beagle dogs against a suspension of free drug (control formulation) all at a dose of 100 mg/kg. Oral administration was conducted in the absence and presence of food. Plasma concentrations and pharmacokinetic parameters were determined within 8 h post-dose. While no measurable absorption of the drug resulted after administration of the control formulation, substantial systemic exposure to the compound was obtained with both kinds of pH-sensitive formulations. The selective release of CGP 70726 in a highly dispersed/amorphous state and creation of high concentrations close to its absorption site was thought to account for this positive result. The largest areas under the plasma concentration-time curve (AUC) were obtained in the fasted state, with slightly better performance of the microparticles over the nanoparticles, in both nutritional states (7.8+/-1.5 versus 5.8+/-0. 8 micromol.h/l in the fasted state; 4.4+/-1.4 versus 2.00+/-0.5 micromol.h/l in the fed state). With these results, the potential of pH-sensitive particles for the oral delivery of HIV-1 protease inhibitors with low water solubility was confirmed.
(S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxi de (S 18986-1) is a new compound that facilitates post-synaptic responses by modulating alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated synaptic responses and thus promotes long-term potentiation and potentiates (S)-AMPA-induced release of noradrenaline in rat brain slices. In the present study, the effects of S 18986-1 were evaluated on cognitive functions by using a one-trial object-recognition test in the Wistar rat, a test which measures a form of episodic memory in rodents. Recognition was measured by the ability of treated rats to discriminate between a familiar and a new object after a 24-h retention delay. Oral administrations with S 18986-1 (0.3 to 100 mg/kg) 1 h before each session of the test improved object recognition at concentrations as low as 0.3 mg/kg. Under the same conditions, the nootropic drug aniracetam was active at a dose of 10 mg/kg by i.p. route. S 18986-1 was still effective on the object-recognition test when it was administered 4 h before each of the three sessions. Furthermore, subchronic oral pretreatment (7 days) with S 18986-1 (0.3 to 30 mg/kg) also increased the recognition of the familiar object indicating that the animals failed to develop tolerance to repeated administrations with S 18986-1. Finally, the recognition of the familiar object was improved when S 18986-1 was administered before the recognition trial whereas the rats failed to recognise the familiar object when S 18986-1 was administered before the sample presentation trial only. Taken together, the results indicated that S 18986-1 facilitated a form of episodic memory in the rat, by improving the recognition of a familiar information (retention). Furthermore, S 18986-1 was long-acting and demonstrated a good oral bioavailability. These data confer on S 18986-1, a potential role in improving episodic memory impaired in neurodegenerative diseases and during aging.