Topic
Methimepip
About: Methimepip is a research topic. Over the lifetime, 5 publications have been published within this topic receiving 76 citations.
Papers
TL;DR: The results suggested that histamine indirectly caused the ERK2 phosphorylation via its effects on the secretion of TNF-α and these effects were mediated via H1, H2, H3, and H4 receptors.
Abstract: Histamine is implicated in allergic disease and asthma and ERK1/2 is involved in allergic inflammation including Th2 differentiation and proliferation. This study was designed to study the effects of histamine on ERK1/2 phosphorylation in splenocytes. C57/BL6 splenocytes were treated with different concentrations of histamine (10−4 to 10−11 M). Histamine (10−4 M) increased ERK2 phosphorylation. There was, however, no significant effect seen at other concentrations (10−11 to 10−6 M). Surprisingly, H1 receptor agonist β-histine (10−5 M), H2 agonist amthamine (10−5 M), H3 agonist methimepip (10−6 M), and H4 agonist 4-methyl histamine (10−6 M), all increased ERK2 phosphorylation. H1R antagonist pyrilamine (10−6 M), H2R antagonist ranitidine (10−5 M), H3/H4R antagonist thioperamide (10−6 M), and H3R antagonist clobenpropit (10−5 M) inhibited histamine-mediated ERK2 phosphorylation suggesting that all four histamine receptor subtypes played some role in this phosphorylation. Because tumor necrosis factor-α (TNF...
13 citations
TL;DR: The present study indicates that, whereas the histamine H(3) receptor is involved in the protection of rat stomach against concentrated HCl, the functional role of the H(4) receptors is still to be defined, although selective agonists induce proulcerogenic effects under HCl challenge.
12 citations
TL;DR: It is suggested that histamine‐induced inhibition of the vagal bradycardic out‐flow in pithed rats is mainly mediated by pre‐junctional activation of histamine H3 receptors, as previously demonstrated for the vasopressor sympathetic out‐flows and the vasodepressor sensory CGRPergic (calcitonin gene‐related peptide) out‐ flow.
Abstract: In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (ACh) release. As vagal release of ACh may be modulated by autoreceptors (muscarinic M2 ) and heteroreceptors (including serotonin 5-HT1 ), this study has analysed the pharmacological profile of the receptors involved in histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre-treated (i.v.) with 1 mg/kg atenolol, followed by i.v. administration of physiological saline (1 ml/kg), histamine (10, 50, 100 and 200 μg/kg) or the selective histamine H1 (2-pyridylethylamine), H2 (dimaprit), H3 (methimepip) and H4 (VUF 8430) receptor agonists (1, 10, 50 and 100 μg/kg each). Under these conditions, electrical stimulation (3, 6 and 9 Hz; 15 ± 3 V and 1 ms) of the vagus nerve resulted in frequency-dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF 8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50 μg/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1-10 μg/kg) was abolished by the H3 receptor antagonist JNJ 10181457 (1 mg/kg, i.v.). In conclusion, our results suggest that histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is mainly mediated by pre-junctional activation of histamine H3 receptors, as previously demonstrated for the vasopressor sympathetic out-flow and the vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow.
5 citations
TL;DR: Data showed that histamine acting through H4 receptors caused the phosphorylation of SAPK/JNK via TNFα, and the role of H 4 receptors in pro-inflammatory response is intriguing.
4 citations
TL;DR: It is observed that N-methyl-substituted immepip (methimepip) exhibits high affinity and agonist activity at the human histamine H(3) receptor and reduces the basal level of brain histamine to about 25% after a 5 mg/kg intraperitoneal administration.
Abstract: In this study, we continue our efforts toward the development of potent and highly selective histamine H3 receptor agonists. We introduced various alkyl or aryl alkyl groups on the piperidine nitrogen of the known H3/H4 agonist immepip and its analogues (1−3a). We observed that N-methyl-substituted immepip (methimepip) exhibits high affinity and agonist activity at the human histamine H3 receptor (pKi = 9.0 and pEC50 = 9.5) with a 2000-fold selectivity at the human H3 receptor over the human H4 receptor and more than a 10000-fold selectivity over the human histamine H1 and H2 receptors. Methimepip was also very effective as an H3 receptor agonist at the guinea pig ileum (pD2 = 8.26). Moreover, in vivo microdialysis (in rat brain) showed that methimepip reduces the basal level of brain histamine to about 25% after a 5 mg/kg intraperitoneal administration.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2016 | 1 |
| 2012 | 1 |
| 2011 | 2 |
| 2005 | 1 |