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 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.
ABT-239 is an H3-receptor inverse agonist developed by Abbott. It has stimulant and nootropic effects, and has been investigated as a treatment for ADHD, Alzheimer's disease, and schizophrenia. ABT-239 is more active at the human H3 receptor than comparable agents such as thioperamide, ciproxifan, and cipralisant. It was ultimately dropped from human trials after showing the dangerous cardiac side effect of QT prolongation, but is still widely used in animal research into H3 antagonists / inverse agonists.
Thioperamide is a potent HRH4 antagonist and selective HRH3 antagonist capable of crossing the blood–brain barrier. It was used by Jean-Charles Schwartz in his early experiments regarding the H3 receptor. Thioperamide was found to be an antagonist of histamine autoreceptors, which negatively regulate the release of histamine. The drug enhances the activity of histaminergic neurons by blocking autoreceptors, leading to greater release of histamine.
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.
Ciproxifan is an extremely potent histamine H3 inverse agonist/antagonist.
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. 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. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.
Dimaprit is a histamine analog working as a selective H2 histamine receptor agonist.
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family — receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
An H3 receptor antagonist is a type of antihistaminic drug used to block the action of histamine at H3 receptors.
A-349,821 is a potent and selective histamine H3 receptor antagonist (or possibly an inverse agonist). It has nootropic effects in animal studies, although there do not appear to be any plans for clinical development at present and it is currently only used in laboratory research.
JNJ-7777120 was 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 (H1) antihistamines in the treatment of pruritus (itching). The drug was abandoned because of its short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies.
4-Methylhistamine is a histamine agonist selective for the H4 subtype.
Impentamine is a histamine antagonist selective for the H3 subtype.
Conessine is a steroidal alkaloid found in a number of plant species from the family Apocynaceae, including Holarrhena floribunda, Holarrhena antidysenterica and Funtumia elastica. It acts as a histamine antagonist, selective for the H3 subtype (with an affinity of pKi = 8.27; Ki = ~5 nM). It was also found to have long CNS clearance times, high blood–brain barrier penetration and high affinity for the adrenergic receptors.
VUF-6002 (JNJ-10191584) is a drug which acts as a potent and selective antagonist at the histamine H4 receptor. It has anti-inflammatory and analgesic effects in animal studies of inflammatory diseases.
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.
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.
VUF-8430 is a histamine agonist selective for the H4 subtype.
UR-AK49 is a drug used in scientific research which acts as a potent antagonist for the Neuropeptide Y / Pancreatic polypeptide receptor Y4, and also as a partial agonist at the histamine receptors H1 and H2. UR-AK49 is a pure antagonist at Y4 with no partial agonist effects, and although it is only slightly selective for Y4 over the related Y1 and Y5 receptors, as the first non-peptide Y4 antagonist developed UR-AK49 is expected to be useful in the study of this receptor and its role in the body.
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.
