H2 antagonists, sometimes referred to as H2RA and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of stomach acid. H2 antagonists can be used in the treatment of dyspepsia, peptic ulcers and gastroesophageal reflux disease. They have been surpassed by proton pump inhibitors (PPIs); the PPI omeprazole was found to be more effective at both healing and alleviating symptoms of ulcers and reflux oesophagitis than the H2 blockers ranitidine and cimetidine.
The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.
Histamine H3 receptors are expressed in the central nervous system and to a lesser extent the peripheral nervous system, where they act as autoreceptors in presynaptic histaminergic neurons, and also control histamine turnover by feedback inhibition of histamine synthesis and release. The H3 receptor has also been shown to presynaptically inhibit the release of a number of other neurotransmitters (i.e. it acts as an inhibitory heteroreceptor) including, but probably not limited to dopamine, GABA, acetylcholine, noradrenaline, histamine and serotonin.
The histamine H4 receptor is, like the other three histamine receptors, a member of the G protein-coupled receptor superfamily.
Histidine decarboxylase (HDC) is an enzyme responsible for catalyzing the decarboxylation of histidine to form histamine. In mammals, histamine is an important biogenic amine with regulatory roles in neurotransmission, gastric acid secretion and immune response. Histidine decarboxylase is the sole member of the histamine synthesis pathway, producing histamine in a one-step reaction. Histamine cannot be generated by any other known enzyme. HDC is therefore the primary source of histamine in most mammals and eukaryotes. The enzyme employs a pyridoxal 5'-phosphate (PLP) cofactor, in similarity to many amino acid decarboxylases. Eukaryotes, as well as gram-negative bacteria share a common HDC, while gram-positive bacteria employ an evolutionarily unrelated pyruvoyl-dependent HDC. In humans, histidine decarboxylase is encoded by the HDC gene.
Cipralisant (GT-2331, tentative trade name Perceptin) is an extremely potent Histamine H3 receptor ligand originally developed by Gliatech. Cipralisant was initially classified as a selective H3 antagonist, but newer research (2005) suggests also agonist properties, i. e. functional selectivity. Cipralisant seemed to be well tolerated during early testing, entering Phase II trials for ADHD in 2000.
Antihistamines are drugs which treat allergic rhinitis and other allergies. Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy. Typically people take antihistamines as an inexpensive, generic, over-the-counter drug with few side effects. As an alternative to taking an antihistamine, people who suffer from allergies can instead avoid the substance which irritates them. However, this is not always possible as some substances, such as pollen, are carried in the air, thus making allergic reactions caused by them generally unavoidable. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Doctors recommend that people talk to them before any longer term use of antihistamines.
Clobenpropit is a histamine H3 receptor antagonist. It has neuroprotective effects via stimulation of GABA release in the brain.
Neurotensin receptor type 2 is a protein that in humans is encoded by the NTSR2 gene.
An H3 receptor antagonist is a classification of drugs used to block the action of histamine at the H3 receptor.
JNJ-7777120 is a drug being developed by Johnson & Johnson Pharmaceutical Research & Development which acts as a potent and selective antagonist at the histamine H4 receptor. It has anti-inflammatory effects, and has been demonstrated to be superior to traditional antihistamines in the treatment of pruritus (itching).
Iodophenpropit is a histamine antagonist which binds selectively to the H3 subtype. Its 125I radiolabelled form is used for mapping the distribution of H3 receptors in the body.
VUF-6002 (JNJ-10191584) is a drug which acts as a potent and selective antagonist at the histamine H4 receptor. It has antiinflammatory and analgesic effects in animal studies of acute inflammation.
GSK-189,254 is a potent and selective H3 histamine receptor inverse agonist developed by GlaxoSmithKline. It has subnanomolar affinity for the H3 receptor (Ki = 0.2nM) and selectivity of over 10,000x for H3 over other histamine receptor subtypes. Animal studies have shown it to possess not only stimulant and nootropic effects, but also analgesic action suggesting a role for H3 receptors in pain processing in the spinal cord. GSK-189,254 and several other related drugs are currently being investigated as a treatment for Alzheimer's disease and other forms of dementia, as well as possible use in the treatment of conditions such as narcolepsy, or neuropathic pain which do not respond well to conventional analgesic drugs.
Amthamine is a histamine agonist selective for the H2 subtype. It has been used in vitro and in vivo to study gastric secretion, as well as other functions of the H2 receptor.
Proxyfan is a histamine H3 receptor ligand which is a "protean agonist", producing different effects ranging from full agonist, to antagonist, to inverse agonist in different tissues, depending on the level of constitutive activity of the histamine H3 receptor. This gives it a complex activity profile in vivo which has proven useful for scientific research.
SCH-79687 is a histamine antagonist selective for the H3 subtype.
Clorotepine, also known as octoclothepin or octoclothepine, is an antipsychotic of the tricyclic group which was derived from perathiepin in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis.
