Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation.

ABSTRACT: Over the years, the cannabinoid type 1 receptor (CB₁R) has emerged as a promising therapeutic target for addressing various neurodegenerative diseases including HIV-associated neurocognitive disorders (HAND). However, the therapeutic application of direct CB₁R activation is often hindered by undesirable psychoactive side effects. To mitigate this issue, research has focused on utilizing positive allosteric modulators (PAMs) to enhance the CB₁R activity indirectly. Preclinical studies have highlighted the efficacy of CB₁R PAMs, such as ZCZ011 and GAT211, in mouse models of Huntington's disease, neuropathic pain, and, more recently, HAND. Building on this evidence, we employed primary frontal cortex neuronal cultures and whole brain microglial cult

SUBMITTER: Yadav TC 

PROVIDER: S-EPMC12531869 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature