Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models.

Background And Purpose: Prolonged use of opioids causes analgesic tolerance and adverse effects including constipation and dependence. Compounds targeting imidazoline I receptors are known to potentiate opioid analgesia in rodents. We investigated whether combination with the I receptor ligand CR4056 could improve efficacy and safety of morphine and explored the mechanisms of the CR4056-opioid interaction.

Increased Total Serum Immunoglobulin E in Children Developing Mycoplasma pneumoniae-related Extra-pulmonary Diseases.

Mycoplasma pneumoniae has been recognized to be involved in several extra-pulmonary diseases, but the underlying immunologic mechanisms are still largely unknown. Recently, we observed a significant elevation of serum Immunoglobulin E (IgE) in a small group of these children. Here, we assessed total serum IgE levels in children affected with Mycoplasma pneumoniae-related extra-pulmonary diseases.

Pharmacological characterisation of CR6086, a potent prostaglandin E receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug.

Background: Prostaglandin E (PGE) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes.

Efficacy of CR4056, a first-in-class imidazoline-2 analgesic drug, in comparison with naproxen in two rat models of osteoarthritis.

Purpose: CR4056, (2-phenyl-6-(1H-imidazol-1yl) quinazoline), an imidazoline-2 (I2) receptor ligand, is a promising analgesic drug that has been reported to be effective in several animal models of pain. The aim of this study was to evaluate the effects of CR4056 in two well-established rat models of osteoarthritis (OA), mimicking the painful and structural components of human OA.

Methods: Knee OA was induced either by single intra-articular injection of monoiodoacetate (MIA) or by medial meniscal tear (MMT) in the right knee of male rats.

Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation.

Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1, 2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1, 2, and 3 have been selected in that, although bearing a common scaffold, preferentially bind to α2-adrenoceptors, imidazoline I2 receptors, or both systems, respectively.