Pharmacologic agents directed at the treatment of pain associated with maladaptive neuronal plasticity.

Introduction: The definition of nociplastic pain in 2016 has changed the way maladaptive chronic pain is viewed in that it may emerge without neural lesions or neural disease. Many endogenous and pharmacologic substances are being investigated for their role in treating the pain associated with neuronal plasticity.

Areas Covered: The authors review promising pharmacologic agents for the treatment of pain associated with maladaptive neuronal plasticity.

Transdermal Buprenorphine for Acute Pain in the Clinical Setting: A Narrative Review.

Transdermal buprenorphine is indicated for chronic pain management, but as its role in the clinical management of acute pain is less clear, this narrative review examines studies of the patch for acute pain, mainly in the postoperative setting. Although perhaps better known for its role in opioid rehabilitation programs, buprenorphine is also an effective analgesic that is a Schedule III controlled substance. Although buprenorphine is a partial agonist at the μ-opioid receptor, it is erroneous to think of the agent as a partial analgesic; it has full analgesic efficacy and unique attributes among opioids, such as a ceiling for respiratory depression and low "drug likeability" among those who take opioids for recreational purposes.

EEG-β/γ spectral power elevation in rat: a translatable biomarker elicited by GABA(Aα2/3)-positive allosteric modulators at nonsedating anxiolytic doses.

Benzodiazepine drugs, through interaction with GABA(Aα1), GABA(Aα2,3), and GABA(Aα5) subunits, modulate cortical network oscillations, as reflected by a complex signature in the EEG power spectrum. Recent drug discovery efforts have developed GABA(Aα2,3)-subunit-selective partial modulators in an effort to dissociate the side effect liabilities from the efficacy imparted by benzodiazepines. Here, we evaluated rat EEG and behavioral end points during dosing of nine chemically distinct compounds that we confirmed statistically to selectively to enhance GABA(Aα2,3)-mediated vs.

Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness.

Sleep disorders (somnipathies) are conditions characterized by disruptions of sleep quality or of sleep pattern. They can involve difficulty falling asleep (prolonged sleep onset latency), difficulty staying asleep (disturbance of sleep maintenance), sleep of poor quality (unrefreshing), or combinations of these and can lead to poor health and quality of life problems. A subtype of sleep-maintenance insomnia is middle-of-the-night wakefulness, a relatively common occurrence.

Development and SAR of functionally selective allosteric modulators of GABAA receptors.

Positive modulators at the benzodiazepine site of α2- and α3-containing GABA(A) receptors are believed to be anxiolytic. Through oocyte voltage clamp studies, we have discovered two series of compounds that are positive modulators at α2-/α3-containing GABA(A) receptors and that show no functional activity at α1-containing GABA(A) receptors. We report studies to improve this functional selectivity and ultimately deliver clinical candidates.

The neuroactive peptide N-acetylaspartylglutamate is not an agonist at the metabotropic glutamate receptor subtype 3 of metabotropic glutamate receptor.

The peptide N-acetylaspartylglutamate (NAAG) is present in high concentrations in the mammalian central nervous system. Various mechanisms have been proposed for its action, including selective activation of the metabotropic glutamate receptor (mGluR) subtype 3, its action at the N-methyl-D-aspartate receptor, or the production of glutamate by its hydrolysis catalyzed by an extracellular protease. To re-examine its agonist activity at mGluR3, we coexpressed human or rat mGluR3 with G protein inward rectifying channels in Xenopus laevis oocytes.