Abstract:
:The histamine H₄ receptor mediates several histamine-induced cellular functions of leukocytes, including cell migration and cytokine production. Recent studies suggest that histamine signaling through the histamine H₄ receptor can also have anti-pruritic and anti-nociceptive functions. 1-(7-(2-amino-6-(4-methylpiperazin-1-yl) pyrimidin-4-yl)-3, 4-dihdroisoquinolin-2(1H)-yl)-2-cyclopentylethanone (INCB38579) is a novel small molecule antagonist of the human and rodent histamine H₄ receptors with at least 80-fold selectivity over the human histamine H₁, H₂ and H₃ receptors, and has good pharmacokinetic properties in rats and mice. The compound is potent in inhibiting histamine binding to and signaling through the recombinant human, mouse and rat histamine H₄ receptors and blocks the histamine-induced migration of human and mouse dendritic cells, as well as the cell shape change and migration of human eosinophils. INCB38579 and histamine may have separate but overlapping binding sites on the human histamine H₄ receptor. This novel inhibitor is efficacious when evaluated in two previously established in vivo models for histamine H₄ receptor activity (histamine-induced itch in mice and carrageenan-induced acute inflammatory pain in rats). When examined in formalin-induced pain models, INCB38579 significantly reduces the sustained inflammatory pain experienced by rats and mice. A good correlation between the protein binding adjusted potency from in vitro studies and its analgesic effect in vivo was observed. These results suggest that INCB38579 can serve as a useful tool for pharmacologic characterization of the histamine H₄ receptor and further support the hypothesis that targeting the histamine H₄ receptor may provide new therapeutic agents for various chronic inflammatory diseases, including inflammatory pain.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Shin N,Covington M,Bian D,Zhuo J,Bowman K,Li Y,Soloviev M,Qian DQ,Feldman P,Leffet L,He X,He Wang K,Krug K,Bell D,Czerniak P,Hu Z,Zhao H,Zhang J,Yeleswaram S,Yao W,Newton R,Scherle Pdoi
10.1016/j.ejphar.2011.11.027subject
Has Abstractpub_date
2012-01-30 00:00:00pages
47-56issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(11)01479-8journal_volume
675pub_type
杂志文章abstract::The number of prolactin (PRL) receptors in the hypothalamus and substantia nigra of aged rabbits is significantly lower than the number measured in young animals. The treatment of aged rabbits for 30 days with S-adenosyl-L-methionine (SAM) restored the number of PRL binding sites to levels found in the hypothalamus an...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90063-0
更新日期:1989-07-18 00:00:00
abstract::Rat aortic smooth muscle rings without endothelial cells were subjected to alpha 1-adrenoceptor stimulation. We measured the contractile state of the smooth muscle cells and the formation of inositol phosphates (InsPs) on receptor stimulation. Using different extracellular calcium-containing solutions (2.5 mM, 0.1 mM ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0922-4106(05)80034-3
更新日期:1991-05-25 00:00:00
abstract::The effects of the treatment with the immunosuppressant deoxyspergualin on the development of experimental autoimmune orchitis were studied. The results showed that C3H/He mice immunized with testicular germ cells and treated daily with either 0.3 or 3 mg/kg body weight deoxyspergualin during days 15-20 post-immunizat...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02045-9
更新日期:2002-08-23 00:00:00
abstract::Luminal exposure of mouse ileal mucosal sheets in vitro to 0.3% Triton X-100 for 10 min resulted in a 45.3 +/- 4.4% decrease in tissue resistance (Rt). Luminal pretreatment of tissue with epidermal growth factor (EGF, 30 nM) reduced the Triton X-100-induced decrease in Rt to 10.2 +/- 3.5%. This effect of luminal EGF w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00186-0
更新日期:1996-05-15 00:00:00
abstract::The purpose of this study was to investigate possible efflux mechanisms involved in amphetamine derivative transport such as for 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), para-methoxyamphetamine (p-MA), dexamphetamine and pseudoephedrine, especially across pH gradients that e...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.06.090
更新日期:2008-09-11 00:00:00
abstract::Carbamazepine moderately depressed the input fiber volley resulting in attenuation of the dendritic epsp and the population spike in CA1 of rat hippocampal slices with a threshold concentration of 20 microM. The depressant effect on the population spike was not antagonized by the adenosine receptor blocker caffeine. P...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90030-5
更新日期:1985-03-26 00:00:00
abstract::The present study was designed to evaluate the preventive effects of p-coumaric acid on lysosomal dysfunction and myocardial infarct size in isoproterenol induced myocardial infarcted rats. Male albino Wistar rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days after which isopr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.11.006
更新日期:2013-01-15 00:00:00
abstract::Depression is a serious mental disorder that is becoming more common. To better treat patients suffering from this illness, elucidation of the underlying psychopathological and neurobiological mechanisms of depression is needed. Based on the evidence, we sought to investigate the effects of hesperidin in a model of de...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.07.042
更新日期:2016-10-15 00:00:00
abstract::Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15 min) protein exudation in different airway tissues, as determined by Evans blue staining. This was associated with marked mast cell degranulation determined by histological examination, with there being no difference between mucosal and con...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01093-7
更新日期:2001-08-24 00:00:00
abstract::Acute respiratory and metabolic acidosis as well as metabolic alkalosis increased (by 11, 11, 21%) whereas respiratory alkalosis antagonized (by 10%) the partial steady state block produced by pipecuronium infusion on the anterior tibialis muscle of the cat. The duration of neuromuscular block following six successive...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90210-5
更新日期:1988-09-23 00:00:00
abstract::The cyclic AMP efflux from rat neostriatal slices induced by simultaneous activation of D-1 (stimulatory) and D-2 (inhibitory) dopamine receptors with 30 microM dopamine was inhibited by morphine (0.3-3 microM), [D-Ala2, D-Leu5]enkephalin (DADLE, 0.03-0.3 microM) but not by [D-Pen2, D-Pen5]enkephalin (DPDPE, 0.03-0.3 ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90150-5
更新日期:1985-12-03 00:00:00
abstract::Neuropathic pain is among the most common and difficult-to-treat types of chronic pain and is associated with sodium channel malfunction. The sodium channel blocker ralfinamide has exhibited potent analgesic effects in several preclinical pain models and in patients with mixed neuropathic pain syndromes (Phase II tria...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.01.041
更新日期:2018-03-15 00:00:00
abstract::The present experiments were devoted to analyzing the mechanisms involved in the captopril-dependent inhibition of human mesangial cell proliferation. Studies were performed in cultured human mesangial cells incubated with captopril, an angiotensin II-converting enzyme inhibitor with antioxidant properties, lisinopril...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01250-8
更新日期:1997-10-08 00:00:00
abstract::The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(89)90045-x
更新日期:1989-03-07 00:00:00
abstract::The in vivo cardiovascular effect and in vitro vasorelaxant effect of harman, one of harmala alkaloids isolated from Peganum harmala, were examined in this study. Harman (1-10 mg/kg, i.v.) dose-dependently produced transient hypotension and long-lasting bradycardia in pentobarbital-anesthetized rats, which were attenu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00928-0
更新日期:2000-03-03 00:00:00
abstract::The open field is a very popular animal model of anxiety-like behavior. An overview of the literature on the action elicited by effective or putative anxiolytics in animal subjected to this procedure indicates that classical treatments such as benzodiazepine receptor full agonists or 5-HT(1A) receptor full or partial ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0014-2999(03)01272-x
更新日期:2003-02-28 00:00:00
abstract::Procaine and procainamide were covalently bound to acryloyl monomers and polymers. The dose-response and time-action parameters of the cardiac antiarrhythmic protection afforded by the prototype drugs and their acryloyl derivatives against chloroform-hypoxia-induced cardiac arrhythmias in unanesthetized mice and epine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90367-x
更新日期:1985-08-27 00:00:00
abstract::We investigated the therapeutic effects of OK432 (picibanil; CAS39325-1-4), an immunomodulator that is derived from the Su strain of Streptococcus pyogenes. This agent was administered alone or combined with human interferon-alpha in a murine model of insulin-dependent diabetes mellitus. Interferon-alpha inhibits vira...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01476-3
更新日期:1998-01-26 00:00:00
abstract::The effects of a single dose of naloxone and of [D-Met2,Pro5]enkephalinamide on the DNA synthesis in the uterus of 7, 14 and 21-day-old rat were studied. After [D-Met2,Pro5]enkephalinamide treatment, an age-dependent decrease in in vitro [3H]thymidine incorporation into DNA was observed in all studied age groups. In t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(95)90132-9
更新日期:1995-10-15 00:00:00
abstract::COVID-19 pandemic presents an unprecedented challenge to identify effective drugs for treatment. Despite multiple clinical trials using different agents, there is still a lack of specific treatment for COVID-19. Having the potential role in suppressing inflammation, immune modulation, antiviral and improving respirato...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2020.173561
更新日期:2020-11-15 00:00:00
abstract::Experimental evidences suggest a role of reactive oxygen species in gentamicin-induced nephropathy in rats. Therefore, we investigated if diallyl disulfide, a garlic-derived compound with antioxidant properties, has a renoprotective effect in this experimental model. Four groups of rats were studied: (1) control, (2) ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01948-4
更新日期:2003-07-18 00:00:00
abstract::We have characterized the tachykinin NK(2) receptor-mediated contraction and vectorial ion transport responses in the muscularis mucosae and mucosa of the rat isolated distal colon, respectively. The tachykinin NK(2) receptor-selective antagonist nepadutant (c([(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta))) p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)00836-6
更新日期:2001-03-01 00:00:00
abstract::Previous results indicated that the rabbit could represent a suitable model for investigations on the functional role of alpha 2-adrenoceptors in fat cells, but the characterization of these receptors was not resolved yet. In the present report, imidazoline compounds were used to attempt a better definition of rabbit ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(90)90010-u
更新日期:1990-04-25 00:00:00
abstract::The interference of azelastine with pleurisy induced by antigen was investigated in actively sensitized rats. The antigenic challenge (ovalbumin, 12 micrograms/cavity) caused early plasma leakage, which peaked within 4 h, accompanied by intense neutrophil infiltration. Pleural exudate decayed 24 h after antigen provoc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90522-r
更新日期:1991-05-17 00:00:00
abstract::In both rats and mice a single large dose of methylenedioxymethylamphetamine (MDMA; 25 mg/kg i.p.) caused a fall 3 h after injection in the content of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, a fall in noradrenaline in hippocampus and cerebellum, and a rise in dopamine (DA) but fal...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90717-0
更新日期:1988-08-02 00:00:00
abstract::In a medium containing 100 mM NaCl and 10 mM MgCl2, the binding of antagonists to rat myocardial muscarinic receptors is well described by the simple Langmuir isotherm. However, in low ionic strength media, while a small proportion of the sites (23%) display a small (2-3 fold) increase in antagonist affinity, the majo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90085-6
更新日期:1981-07-17 00:00:00
abstract::The effects of capsaicin on the ability of platelets to aggregate in response to thrombin, platelet-activating factor or calcium ionophore (A23187) were examined. At concentrations previously shown to activate sensory afferent neurons, capsaicin markedly inhibited the responsiveness of platelets to the three agonists....
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90267-t
更新日期:1991-09-04 00:00:00
abstract::In order to provide further support for a role of central nitric oxide as a mediator of penile erection and yawning, the nitric oxide donors sodium nitroprusside, hydroxylamine, isoamyl nitrite and S-nitroso-N-acetyl-penicillamine were injected into the lateral ventricles (i.c.v.) or into the paraventricular nucleus o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00508-0
更新日期:1995-12-27 00:00:00
abstract::The direct relaxing effect of halothane on airway smooth muscle has been reported to involve the reduction of the cytosolic Ca2+ concentration ([Ca2+]i) and the [Ca2+]i-independent inhibitory mechanism. To clarify the extent of the contribution of these mechanisms, the effect of halothane on the [Ca2+]i-tension relati...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00617-6
更新日期:1996-11-21 00:00:00
abstract::Cannabinoid CB(2) receptors have been implicated in antinociception in animal models of both acute and chronic pain. We evaluated the role both cannabinoid CB(1) and CB(2) receptors in mechanonociception in non-arthritic and arthritic rats. The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(9)THC) was ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.05.024
更新日期:2007-09-10 00:00:00