The drug candidates coming from combinatorial chemistry research and/or the drugs selected from biologically based high-throughput screening are quite often very lipophilic, as these drug candidates exert their pharmacological action at or in biological membranes or membrane-associated proteins. This challenges drug delivery institutions in industry or academia to develop carrier systems for th...

It has now been demonstrated that the μ, δ1 , δ2 , and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR ago...

μ-Opioid receptors are among the most studied G protein-coupled receptors because of the therapeutic value of agonists, such as morphine, that are used to treat chronic pain. However, these drugs have significant side effects, such as respiratory suppression, constipation, allodynia, tolerance, and dependence, as well as abuse potential. Efforts to fine tune pain control while alleviating the s...

The human body is critically dependent on the ventilatory control system for adequate uptake of oxygen and removal of carbon dioxide (CO2). Potent opioid analgesics, through their actions on μ-opioid receptor (MOR) expressed on respiratory neurons in the brainstem, depress ventilation. Opioid-induced respiratory depression (OIRD) is potentially life threatening and the cause of substantial morb...

A prescription is a health-care program implemented by a physician or other qualified practitioner in the form of instructions that govern the plan of care for an individual patient. Although the algorithmic nature of prescriptions is axiomatic, this insight has not been applied systematically to medication safety. We used software design principles and debugging methods to create a "Patient-or...

INTRODUCTION Subutex is a sublingual formulation of buprenorphine that is used to treat opioid dependency. It may be abused parenterally with disastrous consequences. CLINICAL PRESENTATION We present 4 cases of parenteral abuse of Subutex resulting in severe upper limb complications. TREATMENT Two vascular complications were treated with combinations of anticoagulants, vasodilators, brachia...

Opioids are used for acute and chronic pain and dependency. They have a narrow therapeutic index and large interpatient variability in response. Genetic factors regulating their pharmacokinetics (metabolizing enzymes, transporters) and pharmacodynamics (receptors and signal transduction elements) are contributors to such variability. The polymorphic CYP2D6 regulates the O-demethylation of codei...

18 Many analgesic drugs, including mu-opioids, cannabinoids, and the novel non-opioid 19 analgesic improgan, produce antinociception by actions in the rostral ventromedial medulla 20 (RVM). There they activate pain-inhibiting neurons, termed " OFF-cells " , defined by a 21 nociceptive reflex-related pause in activity. Based on recent functional evidence that 22 neuronal P450 epoxygenases are im...

mu-Opioid receptors are the pharmacological targets of endogenous opioid peptides and morphine-like alkaloid drugs. Previous studies of transfected cells and peripheral neurons indicate that opioid receptors are rapidly internalized after activation by the alkaloid agonist etorphine but not after activation by morphine. To determine whether opioid receptors in the central nervous system are reg...