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Regulation of Food Intake01:30

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Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
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Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
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Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
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Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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The Peripheral Cannabinoid Receptor Type 1 (CB1) as a Molecular Target for Modulating Body Weight in Man.

Saoirse Elizabeth O'Sullivan1, Andrew S Yates1, Richard K Porter2

  • 1Artelo Biosciences, Solana Beach, CA 92075, USA.

Molecules (Basel, Switzerland)
|October 23, 2021
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Summary
This summary is machine-generated.

Peripherally restricted cannabinoid 1 (CB1) receptor drugs offer new therapeutic potential for weight management and other conditions by avoiding unwanted central side effects. This approach targets appetite and energy balance effectively.

Keywords:
CB1 receptorappetitebody weightcannabinoiddrug discoverperipheral

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Area of Science:

  • Endocrinology
  • Pharmacology
  • Neuroscience

Background:

  • The cannabinoid 1 (CB1) receptor regulates appetite and body weight.
  • Central CB1 receptor agonists and antagonists have limited therapeutic utility due to side effects.
  • Peripheral CB1 receptor activation influences energy balance, satiety, and gut-brain axis signaling.

Purpose of the Study:

  • To review the mechanisms of peripheral CB1 receptor regulation of body weight.
  • To discuss the therapeutic potential of peripherally restricted CB1 drugs.

Main Methods:

  • Review of existing literature on CB1 receptor pharmacology and physiology.
  • Analysis of the role of peripheral CB1 receptors in energy homeostasis.
  • Examination of clinical development of peripherally restricted CB1 modulators.

Main Results:

  • Peripheral CB1 activation promotes appetite, energy storage, and preservation.
  • Peripherally restricted CB1 agonists and antagonists mitigate central side effects.
  • Peripherally restricted CB1 drugs show promise for obesity, diabetes, alcoholic steatohepatitis, diabetic nephropathy, and pain.

Conclusions:

  • Peripherally restricted CB1 receptor drugs represent a promising next generation of therapeutics.
  • Targeting peripheral CB1 receptors offers a strategy to manage body weight and other conditions effectively.
  • Further development of these peripherally acting compounds is warranted for diverse therapeutic applications.