Virodhamine, an Endocannabinoid, Regulates Neurotransmission

The endogenous cannabinoid system consists of endogenous cannabinoids, cannabinoid receptors, and enzymes that synthesize and degrade endogenous cannabinoids. Specifically, many effects of cannabinoids and endogenous cannabinoids are mediated by two G protein-coupled receptors (GPCR), CB1 and CB2. Besides, CB1 and CB2 mainly bind to inhibitory G protein and are subject to the same pharmacological effects as other GPCRs.

CB1 is the highest expression of GPCR in the human brain. CB1 plays a role in regulating neurotransmission in many brain regions. When it is activated, CB2 regulates immune responses and inflammatory pathways. Furthermore, mice lacking CB2 usually exhibit an increased inflammatory phenotype. There is great interest in the potential role of CB1 in targeting a range of central nervous systems.

Endocannabinoids are substances produced in the body that activate cannabinoid receptors. Importantly, endogenous cannabinoids are relevant to treat various nervous system diseases, such as Alzheimer\’s disease and Parkinson\’s disease. Today, we will introduce an endocannabinoid, Virodhamine.

Virodhamine, an endocannabinoid, regulates neurotransmission.

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From: Sharma DS, Gutti RK, et al. J Cell Physiol. 2021 Feb;236(2):1445-1453.

At first, Virodhamine, an endocannabinoid, regulates neurotransmission by activating the cannabinoid (CB) receptors. Particularly, Virodhamine is an antagonist of the CB1 receptor and an agonist of the CB2 receptor. It induces megakaryocytic differentiation by triggering MAPK signaling and ROS production. Virodhamine has the potential for the research of various neurological disorders such as Alzheimer\’s and Parkinson\’s diseases.

Secondly, Virodhamine increases adherence, membrane expansion, and the size of the nucleus, also, the expression level of CD61 and TRPV1. Interestingly, Virodhamine inhibits the cell proliferation of megakaryocyte cells and significantly increases the portion of high ploidy cells as compared to the control. Virodhamine significantly increases the protein expression level of CB2 receptors. In particular, it significantly increases ROS production and NADPH oxidase NOX4 expression in megakaryocytic cells.

Thirdly, Virodhamine repairs the nicotine and immobilization stress-induced anxiety in vivo. Virodhamine significantly repaired the working memory impairment-like behaviors s at a dose of 5 mg/kg. By the way, Indamine showed significant anxiolytic-like effects against anxiety-like behaviors at a dose of 10 mg/kg.

Finally, Virodhamine is an endocannabinoid with the ability to regulate neurotransmission.

References:

Sharma DS, et al. J Cell Physiol. 2021 Feb;236(2):1445-1453.