Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Feb 2013
Polydatin--a new mitochondria protector for acute severe hemorrhagic shock treatment.
The aim of the study was find out whether neuronal mitochondrial injury does take place in severe shock and to explore effective therapy for severe shock. ⋯ The study shows that neuronal mitochondrial injury is involved in the genesis of severe shock and PD may be the best choice for protection of neuron against mitochondrial injury in severe shock.
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Expert Opin Investig Drugs · Jan 2013
ReviewCombined oral prolonged-release oxycodone and naloxone in chronic pain management.
The use of opioids is associated with unwanted adverse effects, particularly opioid-induced constipation (OIC). The adverse effects of opioids on gastrointestinal function are mediated by the interaction with opioid receptors in the gastrointestinal tract. The most common drugs used for relieving OIC are laxatives, which do not address the opioid receptor-mediated bowel dysfunction and do not provide sufficient relief. ⋯ PR OXN offers a unique and specific mechanism to control OIC in patients receiving chronic opioid therapy. This combination has the potential advantage of preventing OIC, particularly in subgroups of population, like elderly or advanced cancer patients. This approach can decrease the use of laxatives and additional medications, which represent a burden for patients presenting comorbidities requiring multiple medications.
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Expert Opin Investig Drugs · Dec 2012
ReviewJAK2 inhibitors in the treatment of myeloproliferative neoplasms.
Dysregulation of JAK-STAT signaling is a pathogenetic hallmark of myeloproliferative neoplasms (MPNs) arising from several distinct molecular aberrations, including mutations in JAK2, the thrombopoietin receptor (MPL), mutations in negative regulators of JAK-STAT signaling, such as lymphocyte-specific adapter protein (SH2B3), and epigenetic dysregulation as seen with Suppressor of Cytokine Signaling (SOCS) proteins. In addition, growth factor/cytokine stimulatory events activate JAK-STAT signaling independent of mutations. ⋯ Aberrant JAK-STAT signaling is an underlying theme in the pathogenesis of MPNs. While JAK2 inhibitors are active in JAK2V617F and wild-type JAK2 MPNs, JAK2V617F mutation-specific or JAK2-selective inhibitors may possess unique clinical attributes. Complimentary targeting of parallel pathways operating in MPNs may offer novel therapeutic approaches in combination with JAK inhibition. Understanding the intricacies of JAK-STAT pathway activation, including growth factor/cytokine-driven signaling, will open new avenues for therapeutic intervention at known and novel molecular vulnerabilities of MPNs.
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Expert Opin Investig Drugs · Oct 2012
ReviewInsulin and GLP-1 analog combinations in type 2 diabetes mellitus: a critical review.
Glucagon-like peptide-1 (GLP-1) receptor agonists have been used in clinical management of type 2 diabetes since 2005. Currently approved agents were initially developed and approved for combination therapy with oral antidiabetic drugs (OADs). The potential for combined use with insulin has garnered increasing attention due to the potential to reduce side effects associated with insulin therapy and improve glycemic control. ⋯ Limited data currently available from placebo-controlled trials support the use of exenatide twice daily or liraglutide once daily in combination with basal insulin and metformin in subjects with type 2 diabetes unable to attain treatment goals. Several randomized controlled trials are currently studying combinations of insulin with various GLP-1 analogs. Additional guidance on the clinical use of these combinations will likely be forthcoming once these studies are reported. Insulin/GLP-1 analog combinations will require optimization of blood glucose monitoring strategies and delivery systems to decrease the risk of administration errors and reduce the potential complexity of these regimens.
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Expert Opin Investig Drugs · Sep 2012
ReviewTargeting TRPV1 for pain relief: limits, losers and laurels.
With 336 reviews, the capsaicin receptor TRPV1 arguably represent today's most extensively reviewed analgesic target. TRPV1 is strategically located at the peripheral terminals of primary sensory neurons where pain is generated. TRPV1 as a target for analgesic drugs has been validated in preclinical studies. ⋯ Since its discovery in 1997, TRPV1 has run the gamut from excitement to disappointment to cautious optimism. Topical capsaicin has been disappointing for pain relief. By contrast, intrathecal resiniferatoxin is currently undergoing clinical trials in patients with intractable cancer pain. Some of the small-molecule TRPV1 antagonists have successfully passed Phase I safety and tolerability studies in healthy volunteers into Phase II studies to access efficacy in patients. Others showed worrisome unforeseen adverse effects, most important, hyperthermia and impaired noxious heat sensation. We conclude that TRPV1 blockade and desensitization are two promising, complimentary approaches for pain relief. Despite the roadblocks, TRPV1 remains a powerful tool in pain research and a promising therapeutic target.