Clobenpropit dihydrobromide

In vivo study of histamine H4 receptor in immunomodulation.[Pubmed:23137201]

Bratisl Lek Listy. 2012;113(11):641-7.

OBJECTIVE: Recently accumulating evidence has highlighted the role of histamine in inflammation and immune reaction by histamine H4-receptor, however the role of histamine via H4-receptor in immunomodulation is still unclear. Therefore, the present study was designed to study the immunomodulatory role of histamine H4-receptor on antibody generation profile in rabbit. METHODS: The cohort study comprised of 108 rabbits in six groups. Each group consisted of 18 rabbits. Group I (negative control) remained non-immunized and received vehicle (sterile distilled water, 1 mlkg-1 x b.i.d., s.c. for 10 days (3 days prior to immunization until 7 days after immunization)). Group II (positive control) received vehicle (1 mlkg-1 x b.i.d., s.c. for 10 day), while group III-VI received histamine (100 microgkg-1 x b.i.d., s.c.), H4-agonist (Clobenpropit dihydrobromide, 10 microgkg-1 x b.i.d., s.c.), and H4-antagonist (JNJ 7777120, 10 microgkg-1 x b.i.d., i.m.) and DMSO (control group for H4R-antagonist, 1 mlkg-1 x b.i.d., i.m.) respectively for 10 days. Group II-VI were immunized with intravenous injection of sheep red blood cells (SRBC) on day 3. Immunological parameters [immunoglobulins (Ig), immunoglobulin M (IgM), and immunoglobulin G (IgG)] assessed by the whole SRBC-ELISA method and direct hemagglutination assay. RESULTS: Histamine could influence a detectable antibody response to SRBC as early as day 7 postimmunization (post-I), which lasted until day 58 post-I, whereas H4-receptor by H4R-antagonist treatment showed a similar profile of antibody (Ig, IgM, and IgG) generation as the positive control group. On the other hand, H4R-agonist treatment showed immunostimulant activity as compared to other experimental groups. The results were found statistically significant (p<0.01). CONCLUSIONS: Histamine H4-receptor in biological system modulates immunological function and stimulates antibody production only by exogenously administered agonists not by endogenous histamine (Tab. 1, Fig. 3, Ref. 26).

Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor.[Pubmed:14530216]

Br J Pharmacol. 2003 Nov;140(6):1117-27.

1. Histamine (0.004-2 microm) induced a concentration-dependent shape change of human eosinophils, but not of neutrophils or basophils, detected as an increase in forward scatter (FSC) in the gated autofluorescence/forward scatter (GAFS) assay. 2. The histamine-induced eosinophil shape change was completely abolished by thioperamide (10 microm), an H3/H4 receptor antagonist, but was not inhibited by pyrilamine or cimetidine (10 microm), H1 and H2 receptor antagonists, respectively. The H4 receptor agonists, clobenpropit and clozapine (0.004-2 microm), which are also H3 receptor antagonists, both induced eosinophil shape change, which was inhibited by thioperamide (10 microm). The H3/H4 receptor agonists, imetit, R-alpha-methyl histamine and N-alpha-methyl histamine (0.004-2 microm) also induced eosinophil shape change. 3. Histamine induced actin polymerisation (0.015-10 microm), intracellular calcium mobilisation (10-100 microm) and a significant upregulation of expression of the cell adhesion molecule CD11b (0.004-10 microm) in eosinophils, all of which were inhibited by thioperamide (10-100 microm). In addition, the H4 receptor agonist/H3 receptor antagonist clozapine (20 microm) stimulated a rise in intracellular calcium in eosinophils. 4. Activation of H4 receptors by histamine (1 microm) primed eosinophils for increased chemotactic responses to eotaxin, but histamine (0.1-10 microm) did not directly induce chemotaxis of eosinophils. 5. Pertussis toxin (1 microg ml-1) inhibited shape change and actin polymerisation responses induced by histamine showing that these effects are mediated by coupling to a Galphai/o G-protein. 6. This study demonstrates that human eosinophils express functional H4 receptors and may provide a novel target for allergic disease therapy.

Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow.[Pubmed:11179434]

Mol Pharmacol. 2001 Mar;59(3):420-6.

Histamine is a multifunctional hormone that regulates smooth muscle contraction in the airways, acid secretion in the gut, and neurotransmitter release in the central nervous system through three well characterized receptor subtypes, H(1), H(2), H(3), respectively. As part of a directed effort to discover novel G-protein-coupled receptors through homology searching of genomic databases, we identified a partial clone (GPCR105) that had significant homology to the recently identified histamine H(3) receptor cDNA. Expression of the full-length human GPCR105 in cells confers the ability to bind [(3)H]histamine with high affinity (K(D) = 5 nM). GPCR105 is pharmacologically similar to the histamine H(3) receptor in that it binds many of the known H(3) agonists and antagonists, albeit with a different rank order of affinity/potency. GPCR105 does not bind (i.e., K(D) > 10 microM) all tested H(1) and H(2) receptor antagonists such as diphenhydramine, loratadine, ranitidine, and cimetidine, but has modest affinity for the H(2) receptor agonist, dimaprit (377 nM). Whereas the H(3) receptor is expressed almost exclusively in nervous tissues, GPRC105 is expressed primarily in bone marrow and eosinophils. Together, these data demonstrate that GPCR105 is a novel histamine receptor structurally and pharmacologically related to the H(3) receptor. However, its unique expression profile and physiological role suggest that GPCR105 is a fourth histamine receptor subtype (H(4)) and may be a therapeutic target for the regulation of immune function, particularly with respect to allergy and asthma.

Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice.[Pubmed:7957622]

Eur J Pharmacol. 1994 Jul 21;260(1):23-8.

The effect of clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, on electrically induced convulsions was studied in mice. Clobenpropit significantly and dose dependently decreased the duration of each convulsive phase. Its anticonvulsant effects were prevented by pretreatment with (R)-alpha-methylhistamine and imetit (VUF-8325), histamine H3 receptor agonists. These findings suggest that the effect of clobenpropit on electrically induced convulsions is due to an increase in endogenous histamine release in the brain, which is consistent with biochemical results that clobenpropit increased brain histidine decarboxylase activity dose dependently. The anticonvulsive effect of clobenpropit was antagonized by mepyramine, a histamine H1 receptor antagonist, but not by zolantidine, a histamine H2 receptor antagonist, indicating that histamine released by the anticonvulsant effect of clobenpropit interacts with histamine H1 receptors of postsynaptic neurons. The present findings of the effect of clobenpropit on electrically induced convulsions are fully consistent with those of thioperamide as described previously (Yokoyama et al., 1993, Eur. J. Pharmacol. 234, 129), supporting the hypothesis that the central histaminergic neuron system is involved in the inhibition of seizures.

Clobenpropit dihydrobromide is a potent histamine H3R antagonist/inverse agonist with a pEC50 of 8.07 for histamine H3LR. Clobenpropit dihydrobromide acts as partial agonist at histamine H4 receptors (Ki 13 nM). Clobenpropit dihydrobromide also binds to serotonin 5-HT3 receptors (Ki 7.4 nM) and α2A/α2C adrenoceptors (Ki 17.4/7.8 nM). Clobenpropit dihydrobromide increases apoptosis.

Clobenpropit dihydrobromide,145231-35-2,VUF 9153,Natural Products,Histamine Receptor, buy Clobenpropit dihydrobromide , Clobenpropit dihydrobromide supplier , purchase Clobenpropit dihydrobromide , Clobenpropit dihydrobromide cost , Clobenpropit dihydrobromide manufacturer , order Clobenpropit dihydrobromide , high purity Clobenpropit dihydrobromide