An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist.
5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural 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 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, like the other three histamine receptors, is a member of the G protein-coupled receptor superfamily that in humans is encoded by the HRH4 gene.
The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right/below) and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.
The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the OPRL1 gene. The nociceptin receptor is a member of the opioid subfamily of G protein-coupled receptors whose natural ligand is the 17 amino acid neuropeptide known as nociceptin (N/OFQ). This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors. Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease, whereas NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates.
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.
The human muscarinic acetylcholine receptor M5, encoded by the CHRM5 gene, is a member of the G protein-coupled receptor superfamily of integral membrane proteins. It is coupled to Gq protein. Binding of the endogenous ligand acetylcholine to the M5 receptor triggers a number of cellular responses such as adenylate cyclase inhibition, phosphoinositide degradation, and potassium channel modulation. Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor have not been fully explored; however, stimulation of this receptor is known to effectively decrease cyclic AMP levels and downregulate the activity of protein kinase A (PKA).
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.
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.
5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene. Agonists and antagonists for 5-HT receptors, as well as serotonin uptake inhibitors, present promnesic (memory-promoting) and/or anti-amnesic effects under different conditions, and 5-HT receptors are also associated with neural changes.
Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].
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.
VUF-5681 is a potent and selective histamine antagonist which binds selectively to the H3 subtype. However while VUF-5681 blocks the activity of more potent H3 agonists, recent studies suggest that it may have some weak partial agonist activity when administered by itself.
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.
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.
(what is this?) (verify) 