Pharmacokinetics and Safety of a Novel Extended-Release Microsphere Formulation of Risperidone in Patients with Schizophrenia or Schizoaffective Disorder.

Risperidone extended-release injectable suspension (R-ERIS; marketed as RYKINDO) is a novel immediate-release version of risperidone formulated as extended-release microspheres for biweekly intramuscular injection to treat schizophrenia in adults. The pharmacokinetics (PK) and safety of R-ERIS were evaluated in a multicenter, randomized, open-label, multiple-dose study in patients with stable schizophrenia or schizoaffective disorder. Eligible patients (N = 108) 18 to 65 years old were randomized (1:1) to receive IM injections of R-ERIS 25 mg or the comparator, a biweekly risperidone long-acting injectable (BW-RLAI; marketed as RISPERDAL CONSTA) 25 mg for a total of 5 injections.

Escin alleviates cerebral ischemia-induced intestinal pyroptosis via the GR-dependent p38 MAPK/NF-κB signaling and NLRP3 inflammasome activation.

Cerebral ischemia-induced systemic inflammation and inflammasome-dependent pyroptotic cell death in ileum, causing serious intestinal injury. Glucocorticoid receptor (GR) mediates the effects of glucocorticoids and participates in inflammation. Escin has corticosteroid-like, neuroprotective, and anti-intestinal dysfunction effects.

Escin avoids hemorrhagic transformation in ischemic stroke by protecting BBB through the AMPK/Cav-1/MMP-9 pathway.

Background: Hemorrhagic transformation (HT) seriously affects the clinical application of recombinant tissue plasminogen activator (rt-PA). The main strategy for combating HT is to keep the blood-brain barrier (BBB) stable. Escin is the active ingredient of Aesculus hippocastanum and a natural mixture of triterpene saponins, and may play a part in mitigation of HT.

Gβγ subunit inhibitor decreases DOM-induced head twitch response via the PLCβ/IP3/Ca/ERK and cAMP signaling pathways.

Aims: (-)-2,5-dimethoxy-4-methylamphetamine (DOM) induces the head-twitch response (HTR) primarily by activating the serotonin 5-hydroxytryptamine 2A receptor (5-HT receptor) in mice. However, the mechanisms underlying 5-HT receptor activation and the HTR remain elusive. Gβγ subunits are a potential treatment target in numerous diseases.

Effects of natural products on skin inflammation caused by abnormal hormones secreted by the adrenal gland.

The cortex of adrenal gland produces glucocorticoid, mineralocorticoid, and androgen. The medulla of adrenal gland secrets catecholamines. These hormones play an important role in regulating blood pressure, metabolism, and homeostasis of glucose or electrolytes.

The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats.

The aim is to investigate the effect of toludesvenlafaxine (Tdv), a reuptake inhibitor of serotonin, norepinephrine, and dopamine, on the neurological function in cerebral ischemic rats and the underlying mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced in rats and the neuroprotective effects of Tdv were evaluated by infarct size, Garcia test, and beam walking test. Neuronal apoptosis in the peri-infarct area was observed by TUNEL staining.

Identification of a novel heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) ligand that disrupts HnRNPA2B1/nucleic acid interactions to inhibit the MDMX-p53 axis in gastric cancer.

Gastric carcinoma is a highly malignant tumor that still lacks effective molecular targets. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an essential oncogenic driver overexpressed in various cancers. The potential role of hnRNPA2B1 in oncotherapy has not been revealed because of the absence of active chemical molecules.

Escin alleviates stress-induced intestinal dysfunction to protect brain injury by regulating the gut-brain axis in ischemic stroke rats.

Hyperactivity of HPA axis results in intestinal dysfunction, which may play a role in brain injury caused by ischemic stroke (IS). Escin shows a neuroprotective effect but it may not penetrate blood brain barrier (BBB). Previous work in our laboratory showed that escin ameliorated intestinal injury in animals.

Administration of Huperzine A microspheres ameliorates myocardial ischemic injury via α7nAChR-dependent JAK2/STAT3 signaling pathway.

Acetylcholinesterase (AChE) inhibitor (AChEI) is well established as first-line agents for relieving the symptoms of Alzheimer's disease (AD). Injectable sustained-release formulation of AChEI may be suitable for treating AD patients. However, it needs to know whether continuous inhibition of AChE could deteriorate or attenuate myocardial damage if myocardial ischemia (MI) occurs.

Integrated systematic pharmacology analysis and experimental validation to reveal the mechanism of action of Semen aesculi on inflammatory bowel diseases.

Background And Ethnopharmacological Relevance: Semen aesculi (SA), a traditional Chinese herb, has been used in the treatment of gastrointestinal disease for thousands of years. The escin was the main components of SA. A growing number of research showed that escin has a wide range of pharmacological activities in intestinal barrier dysfunction.

The etiology of poststroke-depression: a hypothesis involving HPA axis.

Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead to poor quality of life of patients. There are numerous explanations about the etiologies of PSD.

Continuous Activation of Dopamine Receptors Alleviates LPS-Induced Liver Injury in Mice via β-arrestin2 Dependent Akt/NF-κB Pathway.

Many studies showed that dopamine receptors (DRs) agonists have anti-inflammatory effects. Rotigotine, a non-ergot dopamine receptor agonist, mainly actives DRD2/DRD3/DRD1. Rotigotine extended-release microspheres (RoMS) are a sustained-release formulation that can release sustainably rotigotine for more than 7 days after a single dose of RoMS.

A small-molecule inhibitor of MDMX suppresses cervical cancer cells via the inhibition of E6-E6AP-p53 axis.

Dysfunction of p53 is observed in many malignant tumors, which is related to cancer susceptibility. In cervical cancer, p53 is primarily degradated through the complex of high-risk human papillomaviruses (HPV) oncoprotein E6 and E6-associated protein (E6AP) ubiquitin ligase. What is less clear is the mechanism and role of murine double minute X (MDMX) in cervical carcinogenesis due to the inactive status of murine double minute 2 (MDM2).

Preparation of Long-Acting Somatostatin and GnRH Analogues and Their Applications in Tumor Therapy.

Hormonal drugs are essential treatment options for some hormone-dependent or hormone- sensitive tumors. The common dosage forms of hormonal drugs have a short half-life. Hence, frequent administration is needed, which results in poor patient compliance.

The Use of Herbal Medicines for the Prevention of Glucocorticoid-Induced Osteoporosis.

Glucocorticoids are drugs that are widely used to suppress inflammation and the activation of the immune system. However, the prolonged use or at high doses of glucocorticoid can result in adverse side effects including osteoporosis, bone loss, and an increased risk of fracture. A number of compounds derived from natural plant sources have been reported to exert anti-inflammatory activity by interacting with the glucocorticoid receptor (GR), likely owing to their chemical similarity to glucocorticoids, or by regulating GR, without a concomitant risk of treatment-related side effects such as osteoporosis.

Dopamine, a co-regulatory component, bridges the central nervous system and the immune system.

Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the relationship between the dopaminergic system and neurological-related diseases. However, it has been found recently that DA is an immunomodulatory mediator and many immune cells express dopamine receptors (DRs).

Dopamine receptor agonist rotigotine-loaded microspheres ameliorates sexual function deteriorated by fluoxetine in depression rats.

Low dopamine levels may cause depressive symptoms. Dopamine is also involved in sexual behavior. Rotigotine is a nonergolinic dopamine agonist.

VE-822, a novel DNA Holliday junction stabilizer, inhibits homologous recombination repair and triggers DNA damage response in osteogenic sarcomas.

Homologous recombination repair (HRR) is crucial for genomic stability of cancer cells and is an attractive target in cancer therapy. Holliday junction (HJ) is a four-way DNA intermediate that performs an essential role in homology-directed repair. However, few studies about regulatory mechanisms of HJs have been reported.

Rotigotine-loaded microspheres exerts the antinociceptive effect via central dopaminergic system.

Rotigotine-loaded microspheres (RoMS), a sustained-release formulation with a continuous release of rotigotine for more than 7 days in vivo, have been conducted a clinical trial for the treatment of Parkinson's disease (PD). Previous work from our laboratory showed that RoMS exerted an antinociceptive effect in rat models of inflammatory pain. The purpose of this study was to investigate the mechanisms of action underlying the antinociceptive effect of RoMS.

Lipopolysaccharide/D-galactosamine-induced acute liver injury could be attenuated by dopamine receptor agonist rotigotine via regulating NF-κB signaling pathway.

The pathological of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute liver injury is similar to what is seen clinically, and be mediated by the release of pro-inflammatory mediators. A growing body of studies have shown that dopamine (DA) and DA receptor agonist are associated with inflammation and immune response. Rotigotine, a non-ergoline dopamine receptor agonist, is a drug for the treatment of Parkinson's disease.

Allisartan isoproxil reduces mortality of stroke-prone rats and protects against cerebrovascular, cardiac, and aortic damage.

Stroke is a common cause of death and disability. Allisartan isoproxil (ALL) is a new angiotensin II receptor blocker and a new antihypertensive drug discovered and developed in China. In the present study we investigated the therapeutic effects of ALL in stroke-prone renovascular hypertensive rats (RHR-SP) and the underlying mechanisms.

Role of calcitonin gene-related peptide in pain regulation in the parabrachial nucleus of naive rats and rats with neuropathic pain.

Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats.

Escin ameliorates the impairments of neurological function and blood brain barrier by inhibiting systemic inflammation in intracerebral hemorrhagic mice.

This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased.

The Effect of Rotigotine Extended-Release Microspheres Alone or With Celecoxib on the Inflammatory Pain.

Clinical trials of rotigotine extended-release microspheres (RTGT-MS), which provides a sustained release of rotigotine for near 2 weeks , have been conducted in the treatment of Parkinson's disease (PD). This study was to investigate the analgesic effect of RTGT-MS, and to know whether RTGT-MS have synergistic interaction with non-steroidal anti-inflammatory drug, celecoxib. The inflammatory pain model of rats was prepared by carrageenan-induced paw edema.

Antinociceptive effects of rotigotine-loaded microspheres and its synergistic interactions with analgesics in inflammatory pain in rats.

Rotigotine-loaded microspheres (RoMS) are sustained-release formulations with prolonged anti-Parkinson's effects. Given that pain is a non-motor symptom of Parkinson's disease, this study investigated the antinociceptive effects of RoMS and their synergistic effects with analgesics on inflammatory pain. A model of inflammatory pain was prepared by intraplantarly injecting male Sprague-Dawley rats with carrageenan.