Disease relevance of Tocris-0644

• The results showed that thioperamide, an H3R inverse agonist, increases, whereas imetit, an H3R agonist, decreases appetite and body weight in diet-induced obese (DiO) WT mice [1].
• The inhibition was reversed by micromolar concentrations of the histamine H3 receptor antagonist thioperamide and was sensitive to cholera or pertussis toxin treatment [2].
• The ICV administration of thioperamide (40.8, 122.4, and 408.5 micrograms/10 microL) did not suppress the 4-hour food intake induced by 16-hour fasting; however, thioperamide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-microgram dose of PYY [3].
• 3. R-alpha-MH caused a thioperamide-sensitive fall in mean arterial pressure (MAP) of 8+/-1 mmHg and tachycardia of 18+/-2 bpm (P<0.0005) [4].
• We studied acid variations and plasma gastrin in cats harboring Helicobacter felis, harboring H. pylori, or free of gastric pathogens with reference to thioperamide (H(3) receptor antagonist) and SR-27417A (PAF receptor antagonist) [5].

Psychiatry related information on Tocris-0644

• The sedative effects of oral Sch 50971 was blocked by thioperamide (10 microgram i.c.v.). The sedative activity of Sch 50971 was also examined using EEG activity, locomotor activity and sleep [6].
• Intracerebroventricular histamine (0.5 or 1 nmol/site) or thioperamide (100 nmol/site) also ameliorated 7-chlorokynurenic acid-induced working memory deficits [7].
• In addition, thioperamide reverses the amnesia induced by the post-acquisition treatment with 0.02 mg/kg i.p. of scopolamine (SCOP) [8].
• Pretreatment with thioperamide (4.0 mg/kg) prevented the effects of (R)-alpha-methylhistamine (2.0 micrograms) on slow wave sleep and wakefulness [9].
• Moreover, the inhibitory effects of thioperamide on drinking behavior in water-depleted rats were not mimicked by i.c.v. administration of histamine [10].

High impact information on Tocris-0644

• In cultures with IL-4 plus anti-CD58 mAb, histamine-induced enhancement of IgE and IgG4 production was specifically blocked by thioperamide (H3 receptor antagonist), and was inhibited by anti-IL-10 antibody (Ab) [11].
• Histamine also enhanced IgE and IgG4 production by in vivo-generated sIgE+ and sIgG4+ B cells, respectively, from atopic patients; enhancement was blocked by dimaprit and thioperamide, and was inhibited by anti-IL-6 mAb and anti-IL-10 Ab [11].
• The expression of UCP1 in brown adipose tissue and of UCP3 in brown adipose tissue, white adipose tissue, and skeletal muscle is decreased in H3(-/-) mutants, and the anorexigenic activity of thioperamide is not observed [12].
• Somatostatin antibody increased basal histamine secretion and abolished the decrease in histamine and acid secretion induced by thioperamide, confirming that changes in histamine and acid secretion induced by the activation of H3 receptors reflected changes in somatostatin secretion [13].
• RESULTS: Superfusion with thioperamide (H3 antagonist) increased somatostatin and decreased gastrin and histamine secretion in all three species; superfusion with (r)-alpha-methylhistamine (H3 agonist) had the opposite effect [14].

Chemical compound and disease context of Tocris-0644

• Most importantly, endogenous histamine was released from the anoxic human heart, and thioperamide and clobenpropit each alone increased NE release, indicating that H3R become activated in myocardial ischemia [15].
• Histamine H3 antagonist thioperamide dose-dependently enhances memory consolidation and reverses amnesia induced by dizocilpine or scopolamine in a one-trial inhibitory avoidance task in mice [16].
• Administration of l-histidine (1000 mg/kg) with either thioperamide (5 mg/kg) or metoprine (10 mg/kg) alleviated brain infarction [17].
• On the contrary, the blockade of H(2)-receptors by zolantidine 10 mg/kg reverses both the effect of thioperamide alone and the drug action on the scopolamine-induced memory deficit [8].
• The activity scores recorded on the first cocaine-pairing session were also used to test the effects of thioperamide on cocaine-induced locomotor activity [18].

Biological context of Tocris-0644

• Notably, thioperamide by itself potentiated the capsaicin-evoked increases in heart rate and CGRP overflow (by 25% and 50%, respectively) [19].
• The selective H3-antagonist, thioperamide (5 mg/kg intraperitoneally), significantly enhanced the OA-induced bronchoconstriction with the PD200 value decreased to 4.0 micrograms/kg (p less than 0.001) [20].
• Characterization of the binding site of the histamine H(3) receptor. 2. Synthesis, in vitro pharmacology, and QSAR of a series of monosubstituted benzyl analogues of thioperamide [21].
• Three weeks' thioperamide treatment induced a bilateral HDC mRNA up-regulation in the UVN cats, which was higher than in the untreated UVN group [22].
• Starting from thioperamide, the first potent and selective H3-receptor histamine antagonist, analogues have been synthesized and tested in vitro on rat cerebral cortex to explore structure-activity relationships [23].

Anatomical context of Tocris-0644

• We found that the increase in eosinophil calcium in response to supernatants from anti-IgE-stimulated-HLMC was totally inhibited only when the mast cells were challenged in the presence of indomethacin and MK886, and the eosinophils were preincubated with thioperamide [24].
• Intravenous injection of CCL16 into mice induced a rapid mobilization of eosinophils from bone marrow to peripheral blood, which was also suppressed by thioperamide [25].
• Basophils were co-incubated with anti-IgE (2.6 and 7.8 micrograms/ml) and either the H3 receptor agonist, (R)alpha-methylhistamine (10(-8) and 10(-7) M), or the H3 receptor antagonist thioperamide (10(-6) and 10(-5) M) [26].
• Furthermore, the functional activity of the guanine nucleotide-binding inhibitory protein (G1 protein) was not altered by thioperamide or (R)-alpha-methylhistamine administration in frontoparietal cortical membranes [27].
• Interestingly, when neutrophilia was evoked by carrageenan injection, mast cell depletion and thioperamide had no effect [28].

Associations of Tocris-0644 with other chemical compounds

• The effect of HA was antagonized by selective H2-receptor blockers (tiotidine > oxmetidine > cimetidine = ranitidine) and was not significantly affected by the selective H1- and H3-receptor blockers mepyramine and thioperamide [29].
• Similarly, the H3 receptor antagonist thioperamide (10 microM) blocked the effect of histamine whereas the H1 antagonist mepyramine (1 microM) and the H2 receptor antagonist cimetidine (50 microM) were ineffective [30].
• Further study demonstrated that the protection by thioperamide was due to increased GABA release in NMDA-stimulated samples [31].
• The immobility time of male OF1 mice in the forced swimming test was recorded for 6 min, 1 h after the i.p. administration of R-alpha-methylhistamine (10 and 20 mg/kg), thioperamide (0.2, 2, 10 and 20 mg/kg) or another histamine H3 receptor antagonist, clobenpropit (5 mg/kg) [32].
• 2. The H3-selective antagonist, thioperamide, discriminated between two specific binding sites for [3H]-N alpha-methylhistamine (IC50 1 = 2.75 +/- 0.87 nM, IC50 2 101.6 +/- 12.0 nM, % site 1 = 24 +/- 2%) in 50 mM Tris HCl buffer, but showed homogeneity of binding in 50 mM Na/K phosphate buffer [33].

Gene context of Tocris-0644

• Furthermore, the responses of human and mouse eosinophils to CCL16 were effectively suppressed by thioperamide, an antagonist for H3 and H4 [25].
• Histamine H2 receptor blockade with tiotidine (0.1 microM) slightly decreased, while thioperamide (1 microM), a selective histamine H3 receptor antagonist, did not block histamine-induced dilation [34].
• Tyrosinase was inhibited by the H3 agonist imetit but not by alpha-methylhistamine or the H3 antagonist thioperamide [35].
• The H3 agonist R-alpha-methyl-histamine inhibited, whereas the H3-antagonist thioperamide potentiated gastrin/CCK stimulated histamine release [36].
• The residual 20% neutrophil infiltration seen in mast cell-deficient and MyD88(-/-) mice was not further reduced by thioperamide [28].

Analytical, diagnostic and therapeutic context of Tocris-0644

• Intraperitoneal injection of an H3 antagonist (thioperamide) increased histamine output in mesenteric lymph and stimulated intestinal ornithine decarboxylase activity [37].
• Systemic administration of either thioperamide (5 mg/kg, i.p.), a selective H3 receptor antagonist, or metoprine (10 mg/kg, i.p.), an inhibitor of HA-N-methyltransferase, caused an approximately twofold increase in the HA output 30-60 min after treatment [38].
• 5. Thioperamide-induced antinociception was completely prevented by pretreatment with a non-hyperalgesic i.p. dose of (R)-alpha-methylhistamine in the mouse hot plate and abdominal constriction tests [39].
• Autoradiography of sagittal and frontal sections evidenced specific labelling in a number of gray matter areas over a very low background, as determined using thioperamide, a selective H3-receptor antagonist, as competing drug [40].
• Although highly potent H3 antagonists such as thioperamide lacked antinociceptive activity, homologs of burimamide and thioperamide containing N-aromatic substituents retained H3 antagonist activity and also showed potent, effective analgesia [41].

References