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Histamine H3 receptors are attractive targets for medicine. This is because of their regulatory role in neurotransmission in the central nervous system. The histamine H3 receptor is a G protein-coupled receptor that can potentially be used to treat conditions like ADHD, dementia, schizophrenia, alongside sleep disorders. The impact on obesity is of particular interest. The histamine system is not well understood but it is known to be involved in weight gain. This therefore presents a novel method of combating the condition through the H3 receptors and their antagonists. This paper explores the implications of H3 receptor antagonists in therapeutic conditions.
Here is the full scientific article if you wish to download it.
This paper is of interest to us as endocannabinoid receptors are also G protein-coupled receptors. This family of receptors makes up the target of around 34% of medical drugs. Medical cannabis compounds, CBD and THC, interact with the human endocannabinoid system to produce effects that also modulate ADHD, schizophrenia, sleep disorders, dementia, along with many other areas. As in each condition and circumstance, each individual’s response to medicines will differ, combined therapies can often produce useful treatment and management methods.
The range of applications that H3 receptor antagonists have in therapies is enormous. Many laboratories have cloned and studied different H3 receptor antagonists in a wide variety of animal models, from cognition and sleep to obesity. Because the H3 receptors have been found to play a role in many common disorders, it is hoped that they can be used for treating conditions in humans like attention deficit hyperactivity disorder, cognitive disorders, neurodegeneration, schizophrenia, and more.
H3 receptors are found in most tissues in the body and are involved in dozens of metabolic and signaling processes, opening them up as potential therapeutic pathways for the treatment of human disease.
There is no clinical data available for humans yet. A significant number of laboratories however have reported success in developing H3 clones, receptor antagonists, and models of their action. The complexity of the molecular pathways is becoming clear, but it will be some time before the whole picture is understood. Because of the lack of understanding, it will be difficult to make effective medicines at this time.
Of particular interest is the role of histamine in diet and weight regulation. The paper highlights the role of the H3 receptors in body weight. There are only two drugs approved by the FDA for treating obesity. It is hoped that several of the H3 antagonists that have shown promise in animal models could help with humans. The histamine system is largely the same between humans and most lab animals, so the possibility of successful crossover is quite exciting.
One H3 receptor, thioperamide, “showed that indeed appetite and/or the amount of food consumption was decreased”. Another two (NNC 38-1049 and NNC 38-1202), have been found to “reduce food intake in a dose-dependent manner”.
A drug that directly affects appetite instead of increasing the metabolic rate or other weight loss methods is preferable to most of these. This is due to the possibility of fewer side effects. These studies were performed on rodents in laboratories, how humans react is still to be seen.
The aforementioned complexity of the histamine system and weight loss means that a drug that affects the H3 receptor but only in the way that a patient needs will be difficult. The H3 receptors are involved in many processes and are affected by myriad factors which can alter how they interact. A drug that binds to a H3 receptor and produces the effect that is required is likely to have other effects as well, so extensive testing will be required.
Drugs that directly interact with the H3 receptors are still years away. Preclinical data points to them being effective and relatively safe, but there need to be large-scale double-blind control trials in humans to establish the actual effects and efficacy of these drugs.
In summary, this paper describes how the complexity and interconnectedness of histamine receptors and antagonists that have been discovered makes it very difficult to adapt them into safe drugs. While there is data that implicate the H3 receptors in many conditions, their exact roles are not understood. Clinical trials need to be carried out, until then, it is only hypothesis.