Deutetrabenazine Provides Long-Term Benefit for Tardive Dyskinesia Regardless of Underlying Condition and Dopamine Receptor Antagonist Use: A Post Hoc Analysis of the 3-Year, Open-Label Extension Study.

Background: Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.

Methods: Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794).

Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease.

Introduction: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted.

Methods: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD).

Patient and Healthcare Professional Preferences for Characteristics of Long-Acting Injectable Antipsychotic Agents for the Treatment of Schizophrenia.

Introduction: Studies evaluating patient and healthcare professional (HCP) preferences regarding long-acting injectable (LAI) antipsychotic agent attributes are lacking.

Methods: Surveys were administered to physicians, nurses, and patients who had at least two experiences with TV-46000, an investigational subcutaneous LAI antipsychotic agent for the treatment of schizophrenia, as part of the SHINE study (NCT03893825). Survey topics included preferences for route of administration, potential LAI dosing intervals (once-weekly, twice a month, once a month [q1m], every 2 months [q2m]), injection location, ease of use, syringe type, needle length, and need for reconstitution.

Long-Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia.

Objectives: To assess long-term safety and efficacy of deutetrabenazine in younger (<55 years) and older (≥55 years) adult participants with tardive dyskinesia (TD).

Design: Three-year, single-arm, open-label extension (OLE) study enrolling participants who completed the 12-week, pivotal ARM-TD or AIM-TD studies.

Setting: Seventy-six centers in the United States and Europe.

Repeated social stress increases reward salience and impairs encoding of prediction by rat locus coeruleus neurons.

Stress is implicated in psychopathology characterized by cognitive dysfunction. Cognitive responses to stress are regulated by the locus coeruleus-norepinephrine (LC-NE) system. As social stress is a prevalent human stressor, this study determined the impact of repeated social stress on the relationship between LC neuronal activity and behavior during the performance of cognitive tasks.

Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.

Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity.

The stereoisomer (+)-naloxone potentiates G-protein coupling and feeding associated with stimulation of mu opioid receptors in the parabrachial nucleus.

Classically, opioids produce their effects by activating Gi-proteins that inhibit adenylate cyclase activity. Previous studies proposed that mu-opioid receptors can also stimulate adenylate cyclase due to an initial transient coupling to Gs-proteins. Treatment with ultra-low doses of the nonselective opioid antagonist (-)-naloxone or its inactive enantiomer (+)-naloxone blocks this excitatory effect and enhances Gi-coupling.

A naloxonazine sensitive (mu1 receptor) mechanism in the parabrachial nucleus modulates eating.

The parabrachial nucleus (PBN) is an area of the brain stem that controls eating and contains endogenous opioids and their receptors. Previously, we demonstrated that acute activation of mu opioid receptors (MOPR) in the lateral PBN increased food consumption. MOPRs have been divided operationally into mu(1) and mu(2) receptor subtypes on the basis of the ability of naloxonazine (Nlxz) to block the former but not the latter.

Electrophysiologic effects of systemic and locally infused epibatidine on locus coeruleus neurons.

We evaluated the electrophysiologic response of locus coeruleus neurons to the systemic and local infusion of epibatidine. Rats were anesthetized with 2% halothane and single-unit locus coeruleus discharge was recorded after administration of systemic (2.5, 5 and 10 microg/kg subcutaneously) and intracoerulear (0.

The locus coeruleus nucleus as a site of action of the antinociceptive and behavioral effects of the nicotinic receptor agonist, epibatidine.

The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the locus coeruleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the locus coeruleus (LC), and after subcutaneous administration.

The dorsal raphe nucleus as a site of action of the antinociceptive and behavioral effects of the alpha4 nicotinic receptor agonist epibatidine.

The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the dorsal raphe and after subcutaneous administration.