Tolerance development after successful long-term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamaze...

Previous studies from our laboratory and others have implicated a critical role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, in...

Introduction: The GABAergic system of the brain plays a key role in morphine tolerance and sensitization. As isoniazid is a modulator of the GABAergic system, the present study aims to understand whether isoniazid can influence the induction of tolerance and sensitization to the rewarding effects of morphine.  Methods: The rewarding effects of morphine and isoniazid were assessed using a Condi...

Background: Chronic obstructive pulmonary disease (COPD) is usually considered one of the leading causes of death worldwide, so finding proper therapeutic strategies for this disease is of high importance. In this meta-analysis, we reviewed the existing literature on the efficacy and safety of conventional long acting beta agonists (LABAs) in COPD patients. Methods: We searched MEDLINE and G...

Considerable clinical successes have been achieved in cancer treatment since the introduction of targeted therapies. However, almost inevitably tumors develop therapy resistance, which limits durable clinical responses. Tumors are often heterogeneous, and as a result, therapy-resistant cells are present even before the start of treatment. Resistance is commonly mediated via genetic changes. How...

Studies using core temperature (T(c)) have contributed greatly to theoretical explanations of drug tolerance and its relationship to key features of addiction, including dependence, withdrawal, and relapse. Many theoretical accounts of tolerance propose that a given drug-induced psychobiological disturbance elicits opponent responses that contribute to tolerance development. This proposal and i...

OBJECTIVES There is an urgent need for drugs that hasten sterilization in tuberculosis; however, we presently lack indicators of this activity to guide early drug development. We previously described a novel in vitro assay to study mycobacterial phenotypic drug tolerance, in which sterilizing activity could be assessed. OPC-67,683 is a novel imidazooxazole that accelerates sterilization in the ...

An iron-catalysed cascade synthesis of pyrroles from nitroarenes was developed. The homogeneous catalyst shows remarkable activity at room temperature. Its wide functional group tolerance enables late-stage functionalization drug(-like) molecules.

Drug resistance is a significant obstacle to effective cancer treatment. develops from initially reversible drug-tolerant cells, which offer therapeutic opportunities impede relapse. The mechanisms of proteasome inhibitor (PI) therapy have been investigated intensively, however the ways by cells orchestrate their adaptive responses drug challenges remain largely unknown. Here, we demonstrated t...