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Other names | BIBP-3226 |
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Formula | C27H31N5O3 |
Molar mass | 473.577 g·mol−1 |
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BIBP-3226 is a drug used in scientific research which acts as a potent and selective antagonist for both the Neuropeptide Y receptor Y1 [1] and also the neuropeptide FF receptor. [2] It was the first non-peptide antagonist developed for the Y1 receptor and has been widely used to help determine its functions in the body. Activation of Y1 is thought to be involved in functions such as regulation of appetite [3] and anxiety, [4] and BIBP-3226 has anxiogenic [5] and anorectic effects, as well as blocking the Y1-mediated corticotropin releasing hormone release. [6] It has also been used as a lead compound to develop a number of newer more potent Y1 antagonists. [7] [8]
Corticotropin-releasing hormone (CRH) is a peptide hormone involved in stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis.
The arcuate nucleus of the hypothalamus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate.
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.
Neuropeptide Y receptors are a family of receptors belonging to class A G-protein coupled receptors and they are activated by the closely related peptide hormones neuropeptide Y, peptide YY and pancreatic polypeptide. These receptors are involved in the control of a diverse set of behavioral processes including appetite, circadian rhythm, and anxiety.
Signaling peptide receptor is a type of receptor which binds one or more signaling peptides or signaling proteins.
The neuropeptide FF receptors are members of the G-protein coupled receptor superfamily of integral membrane proteins which bind the pain modulatory neuropeptides AF and FF. The Neuropeptide FF receptor family is a member of the G protein-coupled receptor superfamily containing two subtypes, NPFF1 and NPFF2, which exhibit a high affinity for Neuropeptide FF (NPFF) peptides. NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density, particularly in mammals in the superficial layers of the spinal cord where it is involved in nociception and modulation of opioid functions. These receptors participate to the modulation of opioid receptor function in the brain and spinal cord, and can either reduce or increase opioid receptor function depending which tissue they are released in, reflecting a complex role for neuropeptide FF in pain responses.
Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF2, that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF2 receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH.
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.
Neuropeptide Y receptor type 1 is a protein that in humans is encoded by the NPY1R gene.
Neuropeptide Y receptor type 5 is a protein that in humans is encoded by the NPY5R gene.
Pancreatic polypeptide receptor 1, also known as Neuropeptide Y receptor type 4, is a protein that in humans is encoded by the PPYR1 gene.
NPFF Neuropeptide FF (FLFQPQRFa) is a mammalian amidated neuropeptide originally isolated from bovine brain and characterized as a pain-modulating peptide, with anti-opioid activity on morphine-induced analgesia.
Antalarmin (CP-156,181) is a drug that acts as a CRH1 antagonist.
CP-154,526 is a potent and selective antagonist of the corticotropin releasing hormone receptor 1 developed by Pfizer.
BIIE-0246 is a drug used in scientific research which acts as a potent and selective antagonist for the Neuropeptide Y receptor Y2. It was one of the first non-peptide Y2-selective antagonists developed, and remains among the most widely used tools for studying this receptor. It has been used to demonstrate a role for the Y2 subtype as a presynaptic autoreceptor limiting further neuropeptide Y release, as well as modulating dopamine and acetylcholine release. It has also been shown to produce several behavioural effects in animals, including reducing alcohol consumption in addicted rats and anxiolytic effects, although while selective Y2 agonists are expected to be useful as anorectics, BIIE-0246 did not appear to increase appetite when administered alone.
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.
Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas. NPS binds specifically to a G protein-coupled receptor, NPSR. Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear. It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway, and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.
Neuropeptide VF precursor, also known as pro-FMRFamide-related neuropeptide VF or RFamide-related peptide precursor, is a propeptide that in mammals is encoded by the NPVF (or RPFP) gene. The NPVF gene, and thus the propeptide, are expressed in neurons in the mediobasal hypothalamus. The propeptide is cleaved to form three other peptides, which are: