A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profiles of Y-3 in Healthy Adult Volunteers in the United States

The goal of this clinical trial is to assess the safety, tolerability, and pharmacokinetic profiles of Y-3 in healthy adult volunteers in the United States. The main questions it aims to answer are:
* What the pharmacokinetic profiles of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers?
* If drug Y-3 (40mg and 60 mg) is safe and tolerate in the US healthy adult volunteers.
Researchers will compare drug Y-3 (40 mg and 60 mg) to a placebo (a look-alike substance that contains no drug) to see what the pharmacokinetic profiles of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers and if drug Y-3 (40mg and 60 mg) is safe and tolerate in the US healthy adult volunteers.
Participants will:
* Take drug Y-3 (40 mg) or Y-3 (60 mg) or a placebo only once.
* Answer questions regarding your medical history.
* Comply with the study procedures and requests.
* Complete all tests and collections of PK Sampling.
* Must not have any special dietary requirements and be able to consume the food (low-fat) provided by Tranquil Clinical Research during your 4-night stay.
* Must avoid excessive ( > 8 cups per day) caffeine consumption (i.e. coffee or tea) during your time in the study.
* Must not consume any food or beverage rich in grapefruit, papaya, or mango during your time in the study.
* Must not take any other medications, including traditional Chinese medicines and herbal medicines, during your time in the study.
* Must avoid sexual activity or use non-drug contraceptive measures (i.e. condoms) during your time in the study.
* Female participants must not become pregnant while in the study.
* Must not receive any vaccinations during your time in the study.
* Must not donate blood for purposes outside of study procedures during your time in the study.
* Must not drink alcohol during your time in the study.
* Must not smoke during your time in the study.
* Inform your Study Doctor if you no longer wish to participate in the study.

Start Date06 Jan 2025

Sponsor / Collaborator

Neurodawn Pharmaceutical Co., Ltd.

CTR20242311

/ RecruitingPhase 3

注射用Y-3治疗急性缺血性卒中III期临床试验——多中心、随机、双盲、平行、安慰剂对照III期临床研究

[Translation] Phase III clinical trial of Y-3 injection in the treatment of acute ischemic stroke - a multicenter, randomized, double-blind, parallel, placebo-controlled phase III clinical study

评价注射用Y-3治疗发病在48h以内的急性缺血性卒中患者的有效性和安全性

[Translation]

To evaluate the efficacy and safety of Y-3 for injection in the treatment of patients with acute ischemic stroke within 48 hours of onset

Start Date24 Jul 2024

Sponsor / Collaborator

Neurodawn Pharmaceutical Co., Ltd.

NCT06517173

/ RecruitingPhase 3IIT

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Y-3 in Chinese Subjects with Acute Ischemic Stroke

This trial aims to evaluate the effectiveness and safety of Y-3 for injection in the treatment of patients with acute ischemic stroke within 48 hours of onset

Start Date24 Jul 2024

Sponsor / Collaborator

Beijing Tiantan Hospital

[+1]

100 Clinical Results associated with PSD95 x nNOS

100 Translational Medicine associated with PSD95 x nNOS

0 Patents (Medical) associated with PSD95 x nNOS

177

Literatures (Medical) associated with PSD95 x nNOS

01 May 2025·Neurobiology of Stress

The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats

Article

Author: Li, Xinyu ; Lu, Tong ; Wang, Yuxue ; Sun, Xuehan ; Sun, Haiji ; Li, Yuanyuan ; Zhao, Dongqin ; Wang, Zepeng ; Ma, Xiaoli

Previous studies have shown that acute stress-induced gastric mucosal damage is linked to excessive activation of parasympathetic nervous system. The Insular Cortex (IC), the higher centers of the parasympathetic nervous system, serves as both the integration site of gastric sensory information and play a crucial role in the regulation of gastric function. However, whether the IC is involved in Restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of neuronal c-Fos, PSD95 and SYN-1 protein expression in IC during RWIS by immunofluorescence and western blot techniques, as well as assessed IC blood oxygenation level dependant (BOLD) through functional MRI. Chemical genetics techniques specifically modulate the activity of IC glutamatergic neurons and IC-nucleus tractus solitary (NTS) glutamatergic pathway to elucidate their contributions to RWIS-induced gastric mucosal damage. The results showed that the expression of c-Fos, PSD95, and SYN-1 protein in IC increased significantly after RWIS, along with a noticeable enhancement in fMRI signal intensity. Furthermore, inhibiting IC glutamatergic neurons and the IC-NTS glutamatergic neural pathway resulted in a significant reduction in gastric mucosal damage, an increase in the expression of Occludin, Claudin-1, and PCNA in the gastric wall, while the expression of nNOS decreased and CHAT increased. These findings suggest that during RWIS, IC glutaminergic neurons are activated, promoting stress-induced gastric mucosal damage through the IC-NTS-vagal nerve pathway.

01 Mar 2025·Molecular Neurobiology

PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain

Review

Author: Li, Jing ; Yuan, Jie ; Cao, Song ; Ma, Lulin ; Tan, Xinran ; Wen, Song ; Sun, Dongdong

Chronic pain, as a social public health problem, has a serious impact on the quality of patients' life. Currently, the main drugs used to treat chronic pain are opioids, antipyretic, and nonsteroidal anti-inflammatory drugs (NSAIDs). But the obvious side effects limit their use, so it is urgent to find new therapeutic targets. Postsynaptic density (PSD)-95 protein plays an important role in the occurrence and development of chronic pain. The over-expression of the PSD-95 protein and its interaction with other proteins are closely related to the chronic pain. Besides, the PSD-95-related drugs that inhibit the expression of PSD-95 as well as the interaction with other protein have been proved to treat chronic pain significantly. In conclusion, although more deep studies are needed in the future, these studies indicate that PSD-95 and the related proteins, such as NMDA receptor (NMDAR) subunit 2B (GluN2B), AMPA receptor (AMPAR), calmodulin-dependent protein kinase II (CaMKII), 5-hydroxytryptamine 2A receptor (5-HT2AR), and neuronal nitric oxide synthase (nNOS), are the promising therapeutic targets for chronic pain.

01 Mar 2025·The Journal of Pharmacology and Experimental Therapeutics

Agmatine inhibits NMDA receptor–mediated calcium transients in mouse spinal cord dorsal horn via intact PSD95-nNOS signaling

Article

Author: Kitto, Kelley F ; Vulchanova, Lucy ; Fairbanks, Carolyn A ; Florio, Stephanie K ; Schorn, Rachel E ; Wilcox, George L ; Peterson, Cristina D ; Xie, Tongzhen

Intrathecal administration of agmatine, an NMDA receptor (NMDAr) antagonist and nitric oxide synthase inhibitor, prevents neuropathic pain behavior in a dose-dependent manner by acting at the GluN2B subunit of the NMDAr. The present study investigated the pharmacological mechanism of agmatine's inhibitory effect using calcium imaging and an in vivo assay of nociceptive responses induced by NMDA. The application of NMDA-evoked calcium transients in the mouse spinal cord dorsal horn slice was inhibited by the NMDAr antagonist, 2-amino-5-phosphonovalerate. Agmatine also concentration-dependently inhibited NMDA-evoked calcium responses. To evaluate the role of the GluN2B subunit of the NMDAr in the agmatine response, we conditionally knocked-down Grin2B, the gene encoding GluN2B, in spinal cord dorsal horn neurons (GluN2B knockdown [GluN2B-KD]). In control spinal cord slices, ifenprodil inhibited NMDAr-mediated calcium transients, but it was not effective in GluN2B-KD. Surprisingly, agmatine was equally effective in reducing calcium transients in control and GluN2B-KD mouse spinal cord slices. To determine whether the effect of agmatine could be attributed to an action downstream of the NMDAr (eg, neuronal nitric oxide synthase [nNOS]), we used the PSD95-nNOS tethering inhibitor, IC87201, to disrupt the link between NMDAr and nNOS. In the presence of IC87201, agmatine's attenuation of NMDA-evoked calcium transients in ex vivo spinal cord dorsal horn was significantly reversed as was agmatine's antihyperalgesic effect in the intrathecal NMDA-evoked thermal hyperalgesia in vivo model. These results indicated that agmatine requires an intact NMDAr-PSD95-nNOS pathway to attenuate NMDAr-mediated calcium transients and thermal hyperalgesia induced by intrathecal NMDA. SIGNIFICANCE STATEMENT: Chronic pain is an urgent public health concern, and effective long-term treatments are still needed. Agmatine reduces pain in preclinical models without the side effects of motor dysfunction or addiction. Clarifying the pharmacological mechanism of agmatine's analgesic effect in spinal neurotransmission may facilitate the development of novel pain-alleviating therapeutics.

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