The development of safe and effective drugs relies on the discovery of selective ligands. Serotonin (5-hydroxytryptamine [5-HT]) G protein-coupled receptors are therapeutic targets for CNS disorders but are also associated with adverse drug effects. The determination of crystal structures for the 5-HT1B and 5-HT2B receptors provided an opportunity to identify subtype selective ligands using structure-based methods. From docking screens of 1.3 million compounds, 22 molecules were predicted to be selective for the 5-HT1B receptor over the 5-HT2B subtype, a requirement for safe serotonergic drugs. Nine compounds were experimentally verified as 5-HT1B-selective ligands, with up to 300-fold higher affinities for this subtype. Three of the ligands were agonists of the G protein pathway. Analysis of state-of-the-art homology models of the two 5-HT receptors revealed that the crystal structures were critical for predicting selective ligands. Our results demonstrate that structure-based screening can ...

J:60039 Sarhan H, et al., 5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes: further evidence using 5-HT moduline, polyclonal 5-HT1B receptor antibodies and 5-HT1B receptor knock-out mice. Naunyn Schmiedebergs Arch Pharmacol. 2000 Jan;361(1):12-8 ...

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Cardiac: The 5-HT2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT2B receptor null mice.[9] The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts,[10] which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy. Moreover, 5-HT2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.[11][12][13] ...

5-HT1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus.[8] The function of the 5-HT1B receptor differs depending upon its location. In the frontal cortex, it is believed to act as a postsynaptic receptor inhibiting the release of dopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin[9] and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency,[10] respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression.[11] When the expression of 5-HT1B in human cortex was traced throughout life, significant changes during adolescence were observed, in a way that is strongly correlated ...

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B

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The major findings of this study are that known valvulopathic 5-HT2B agonists are distinguished by relatively high potencies across a variety of signaling measures and that potent 5-HT2B receptor agonism is a relatively rare occurrence among drugs and drug-like compounds. In addition, our results demonstrate that no single pattern of functional selectivity (Urban et al., 2007) distinguishes bona fide valvulopathic drugs from nonvalvulopathic drugs. On the other hand, a composite analysis of the signaling data indicates that ropinirole (a 5-HT2B agonist not associated with VHD) has a distinctly different pattern of functional selectivity compared with known VHD-inducing medications.. To arrive at these conclusions, we screened a composite library containing three publicly available collections of FDA-approved and investigational medications and one internally compiled library (approximately 2200 compounds in all). After removing nonspecific agonists (false positives) from the initial hit list, ...

Localization of the C3b receptors in human renal glomeruli.: Cryostat sections of human kidney were incubated with C3b containing immune complexes. The complexe

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YM-348 je lek sa indazolnim osnovom koji deluje kao potentan i selektivan agonist 5-HT2C receptor, sa EC50 vrednošću od 1 nM i 15x selektivnošću u odnosu na 5-HT2A. On je umereno selektivan 3x u odnosu na blisko srodni 5-HT2B receptor.[1][2] On ispoljava termogeno i anoreksično dejsto u životinjskim studijama, što ga čini potencijalno korisnim u lečenju gojaznosti.[3][4][5][6] ...

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5-HT1B;5- HT1B; 5-HT-1B; 5-HT-1D-beta; S12; Serotonin 1D beta receptor; Serotonin receptor 1B; 5-hydroxytryptamine 1B receptor 1B Receptor +, 5-Hydroxytryptamine; 1B Receptor +, Serotonin; 1B Receptors +, 5-Hydroxytryptamine; 1Dbeta Receptor +, Serotonin; 5 HT 1B recept; 5 HT1B Receptor; 5 HT1DBETA recept; 5 HT1Dbeta Receptor; 5 Hydroxytryptamine 1B Receptor; 5-HT(1B) Receptor; 5-HT(1Dbeta) Receptor; Receptor serotonin 5 HT 01 B; Receptor +, 5 Hydroxytryptamine 1B; Receptor +, 5-HT1B; Receptor +, 5-HT1Dbeta; Receptor +, 5-Hydroxytryptamine 1B; Receptor +, Serotonin 1B; Receptor +, Serotonin 1Dbeta; Receptor +, Serotonin Type 1Dbeta; Receptors +, 5-Hydroxytryptamine 1B; Receptors +, Serotonin 1Dbeta; Serotonin 01 B receptor; Serotonin 1B recept; Serotonin 1B Receptor; Serotonin 1D BETA recept; Serotonin 1D Beta Receptor Serotonin 1DBETA recept; Serotonin 1Dbeta receptor; + ...

Background 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake. Methods Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration .... ...

Background 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake. Methods Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration .... ...

Axonal release of serotonin (5-hydroxytryptamine, 5-HT) in the CNS is typically regulated by presynaptic 5-HT autoreceptors. Release of 5-HT in substantia nigra pars reticulata (SNr), a principal output from the basal ganglia, has seemed an interesting exception to this rule. The SNr receives one of the highest densities of 5-HT innervation in mammalian brain and yet negative feedback regulation of axonal 5-HT release by endogenous 5-HT has not been identified here. We explored whether we could identify autoregulation of 5-HT release by 5-HT(1B) receptors in rat SNr slices using fast-scan cyclic voltammetry at carbon-fiber microelectrodes to detect 5-HT release evoked by discrete stimuli (50 Hz, 20 pulses) paired over short intervals (1-10 s) within which any autoreceptor control should occur. Evoked 5-HT release exhibited short-term depression after an initial stimulus that recovered by 10 s. Antagonists for 5-HT(1B) receptors, isamoltane (1 microM) or SB 224-289 (1 microM), did not modify release

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BioAssay record AID 473575 submitted by ChEMBL: Antagonist activity at human CCR2B receptor expressed in HEK293 cells assessed as inhibition of MCP1-induced increase in intracellular calcium level at 1 uM.

ウサギ・ポリクローナル抗体 ab102036 交差種: Hu 適用: WB…Lamin B Receptor抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。

By default, all articles on GreenMedInfo.com are sorted based on the content type which best reflects the data which most users are searching for. For instance, people viewing substances are generally most interested in viewing diseases that these substances have shown to have positive influences. This section is for allowing more advanced sorting methods. Currently, these advanced sorting methods are available for members only. If you are already a member, you can sign in by clicking here. If you do not currently have a user account, and would like to create one/become a member, click here to begin the singup process ...

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RS-127,445 je lek koji deluje kao potentan i selektivan antagonist na serotoninskom 5-HT2B receptor, sa oko 1000x selektivnošću u odnosu na blisko srodne 5-HT2A i 5-HT2C receptore.[1] Uloga 5-HT2B receptora u telu još uvek nije dovoljno razjašnjena, i RS-127,445 je bio korisno oruđe u raščlanjavanju funkcija različitih sistema u kojima je ovaj receptor izražen.[2][3][4] ...

AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor with an IC50 of 104 nM。 - Mechanism of Action & Protocol.

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5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines. The 5-HT2B receptor subtype is involved in: CNS: presynaptic inhibition, behavioural effects Vascular: pulmonary vasoconstriction Cardiac: The 5-HT2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT2B receptor null mice. The 5-HT2B receptor stimulation can also lead to pathological ...

A highly selective peptide agonist of the endothelin-B receptor. Endothelin B receptor agonist SPI-1620 binds to endothelin-B receptors on endothelial cells in tumor blood vessels, which, unlike the angioarchitecture of normal blood vessels, are relatively devoid of smooth muscle. This agent may induce a transient, selective increase in blood flow to a tumor, which may result in an increase in the delivery of anticancer agents to the tumor and, so, an increase in anticancer agent efficacy.. ...

Inhibitory neurotransmission is mediated primarily by GABA. The metabotropic GABA(B) receptor is a G protein-coupled receptor central to mammalian brain function. Malfunction of GABA(B) receptor has been implicated in several neurological disorders. GABA(B) receptor functions as a heterodimeric asse …

The results reported here indicate that SSRI does not induce in vivo nerve fiber tract growth across a surgical anastomosis, but MOS-LA and MOS-PO promoted a 5-HT4 receptor-mediated neural regeneration, since effects of MOS-LA and MOS-PO were antagonized by 5-HT4 receptor antagonists GR (see Fig. 2) and SB-207266 (our unpublished data in guinea pigs and mice), respectively. There were no significant differences in nerve fiber tract growth action between MOS-LA and MOS-PO after 2 wk, suggesting that the clinical application of MOS is promising.. SSRI can increase endogenous 5-HT in the gastrointestinal tract (1). Increased endogenous 5-HT can act on enteric neural 5-HT4 receptors as well as other subtypes of 5-HT receptors such as 5-HT3 receptors (14). In fact, there is evidence supporting the idea that a variety of subtypes of 5-HT receptors play roles in the inflammatory response (2, 7, 26). 5-HT3 receptors in in vitro nodose ganglion play proinflammatory roles (7), whereas enteric neuronal ...

TY - JOUR. T1 - F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT(1B/1D) receptors in models relevant to migraine. AU - John, Gareth W.. AU - Pauwels, Petrus J.. AU - Perez, Michel. AU - Halazy, Serge. AU - Le Grand, Bruno. AU - Verscheure, Wan. AU - Valentin, Jean Pierre. AU - Palmier, Christiane. AU - Wurch, Thierry. AU - Chopin, Philippe. AU - Marien, Marc. AU - Kleven, Mark S.. AU - Koek, Wouter. AU - Assie, Marie Bernadette. AU - Carilla-Durand, Elisabeth. AU - Tarayre, Jean Pierre. AU - Colpaert, Francis C.. PY - 1999/7/1. Y1 - 1999/7/1. N2 - F 11356 (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1- yl]benzonitrile) was designed to take advantage of the superior potency and efficacy characteristics of 5-hydroxytryptamine (5-HT) compared with tryptamine at 5-HT(1B/1D) receptors. F 11356 has subnanomolar affinity for cloned human and nonhuman 5-HT(1B) and 5-HT(1D) receptors, and its affinity for 5-HT(1A) ...

Fast delivery of PPP1R3B knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.

Fast delivery of PPP1R3B knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.

The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands of the NR2B receptor and may be useful for the treatment of various disorders of the central nervous system.

Nozulak J, Kalkman HO, Floerscheim P, Hoyer D, Schoeffter P, Buerki HR. (+)-cis-4,5,7a,8,9,10,11,11a-Octahydro-7H-10-methylindolo[1,7-bc][2,6]- naphthyridine: A 5-HT2C/2B Receptor Antagonist with Low 5-HT2A Receptor Affinity. Journal of Medicinal Chemistry. 1995 Jan;38(1):28-33. DOI:10.1021/jm00001a007 ...

This thing might work for some. Proof of its working is thin, but that tends to be a chronic problem with this kind of device. The patients studied with Cefaly had ...

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CO2 anion has which of the characteristics? Bonds of unequal length (A) (C) (B) (D) sp2-hybridised carbon Same bond angles Resonance stabilisation

(KudoZ) English to Polish translation of Data buffer underrun error: błąd opróżnienia/niedopełnienia bufora danych [Computers: Software].

This line is a derivative of L-M(TK-) (see ATCC CCL-1.3) that is stably transfected with the gene for the human adrenergic alpha1B receptor.

The electrical submersible pump, typically called an ESP, is an efficient and reliable artificial-lift method for lifting moderate to high volumes of fluids from wellbores. These volumes range from a low of 150 B/D to as much as 150,000 B/D (24 to 24,600 m 3 /d). Variable-speed controllers can extend this range significantly, both on the high and low side.. Quotation ...

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