BF-1 – A novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs

Schmitz, Beate; Ullmer, Christoph; Segelcke, Daniel; Gwarek, Mirella; Zhu, Xin-Ran; Lübbert, Hermann

doi:10.1016/j.ejphar.2015.01.043

Cited by 20 publications

(19 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They can act on the vascular wall, thus causing the neurogenic inflammatory response and central sensitization of the endocranium. 5‐HT in the central nervous system can bind to its different receptors to affect the release of substrate P and calcitonin gene‐related peptides and mediate the contraction and relaxation of the meningeal vessels, thereby exerting different pain modulation effects . The abnormalities of the content and functions of 5‐HT play important roles in the occurrence and development of VM.…”

Section: Discussionmentioning

confidence: 99%

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Qiu

Wang

et al. 2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Objective To investigate the correlation of 5‐hydroxy tryptamine receptor 6 (5‐HTR6) gene polymorphism with vestibular migraine (VM). Methods A total of 92 VM patients were enrolled as the observation group, and 100 healthy people receiving physical examinations as the control group. Their general clinical information was collected, and the level of 5‐HT in plasma and the vestibular function test indexes were detected. Moreover, the polymorphism of 5‐HTR6 rs770963777 was detected with the TaqMan‐MGB probe. Results The observation group had a lower level of 5‐HT than the control group (P < .05), and the abnormality rates of the vestibular function tests, including the caloric test, head‐shaking test, and vestibular autorotation test, were obviously higher than those in the control group (P < .01). The comparisons showed that the distribution frequencies of the genotypes and alleles were different between the two groups (P < .05). According to the analysis of the genetic mode, there were differences in recessive and additive modes between the two groups (P < .05), but the dominant mode was not different between the two groups (P > .05). Conclusion The level of 5‐HT and the vestibular function test indexes can serve as the effective indicators for observing VM, and the polymorphism of 5‐HTR6 rs770963777 site is correlated with VM onset.

show abstract

Section: Discussionmentioning

confidence: 99%

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Qiu

Wang

et al. 2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…Further, whereas we have reported that over-the-counter drug "NARON ACE ® ", which contained ETZ, exerted very good clinical performance for headache symptoms 1) , there are no studies focused on the pathogenesis of headache. For example, it has been suggested that in the rat model of migraine, the 5HT 2B receptor localized on the vascular endothelial cells of the dura matter has an important role in meningeal neurogenic inflammation 35,36,37) . Furthermore, the 5HT 2B receptor expressed in the trigeminal ganglionic cells of mice 21) could be assumed to have a role in the pain processing of trigeminal afferents.…”

Section: Biological and Pharmaceutical Bulletin Advance Publicationmentioning

confidence: 99%

Ethenzamide Exerts Analgesic Effect at the Spinal Cord <i>via</i> Multiple Mechanisms of Action Including the 5HT<sub>2B</sub> Receptor Blockade in the Rat Formalin Test

Nikaido

Maruyama

Hamanaka

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an over-the-counter (OTC) drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action.Of the 85 receptors, ion channels, transporters and enzymes tested, we found that ETZ binds to the 5-hydroxytryptamine (5HT) 2B receptor in concentration-dependent manner with modest inhibitory effects on monoamine oxidase-A and transient potential vanilloid 1 channel. The 5HT 2B receptor antagonist activity of ETZ was also confirmed in a cellular functional assay. Furthermore, the drug exerted no inhibitory effects on cycrooxygenase-1 and -2. In the rat formalin test, oral administration of ETZ significantly reduced the nociceptive responses of the second phase and also the number of c-Fos-expressing cells in the spinal dorsal horn, in a dose-dependent manner. Moreover, intrathecal administration of ETZ significantly reduced the nociceptive responses. These results suggest that the analgesic effect of ETZ is exerted at least in the spinal cord, and the effect would be attributed to multiple mechanisms of action including 5HT 2B receptor blockade.

show abstract

“…According to the authors these low affinities for the 5-HT 2C receptor and the H1 receptor preclude unspecific effects, which appeared to be more prominent with older substances, e.g. pimethixene (1-methyl-4-(9H-thioxanthen-9-ylidene) piperidine (pki ¼ 10.14 for H1 receptors and 8.42 for 5-HT 2C receptors) (8). The inhibition of 5-HT 2B receptors with the compound RS-127445, a selective, high-affinity (pki ¼ 9.5), orally bioavailable 5-HT 2B receptor antagonist (30), was shown to inhibit the mCPP-induced PPE as well as c-fos expression in the rat trigeminal nucleus caudalis (TNC) evoked by capsaicin (31).…”

Section: The Acute Activation Of 5-ht 2b Receptors Leads To Neurogenimentioning

confidence: 99%

“…Experimental data show that particularly 5-HT 2B receptors play a role in functions that may be associated with the pathophysiology of headaches. Acute activation of 5-HT 2B receptors by mCPP led to nitric oxide (NO)-dependent plasma protein extravasation (PPE) in the dura mater of guinea pigs (8,9) and activation of neurons in the trigeminal nucleus caudalis (TNC) of rats (10). Therefore it has been assumed that meningeal 5-HT 2B receptors are involved in early steps of migraine pathogenesis (11).…”

Section: Introductionmentioning

confidence: 99%

Putative role of 5-HT_2B receptors in migraine pathophysiology

Segelcke

Meßlinger

2016

Cephalalgia

Self Cite

View full text Add to dashboard Cite

Objective In this review we attempt to characterize the acute and chronic role of 5-HT receptors with regard to meningeal nociception in animal experiments and clinical data targeting migraine therapy. Background Migraine is a common disabling neurovascular primary headache disease, the pathomechanism of which is still unclear. Serotonin (5-HT) and its receptors might play an important role in some aspects of migraine pathogenesis. The ability of the unselective 5-HT receptor agonist m-chlorophenylpiperazine to induce migraine attacks in migraine sufferers, the high affinity of prophylactic antimigraine drugs to this receptor and its expression in migraine-relevant structures like the dura mater argue for a role of 5-HT receptors in the pathogenesis of migraine attacks. Methods For this review, the relevant databases such as PubMed, MEDLINE®, Cochrane Library and EMBASE, respectively, were searched to December 2015 using the keywords "migraine, 5-HT, trigeminal, neurogenic inflammation, nitric oxide, nitroxyl, vasodilatation, plasma protein extravasation" and combinations thereof. Conclusion Our literature review suggests an important role of 5-HT receptor activation in meningeal nociception and the generation of migraine pain.

show abstract

BF-1 – A novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs

Cited by 20 publications

References 21 publications

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Ethenzamide Exerts Analgesic Effect at the Spinal Cord <i>via</i> Multiple Mechanisms of Action Including the 5HT<sub>2B</sub> Receptor Blockade in the Rat Formalin Test

Putative role of 5-HT_2B receptors in migraine pathophysiology

Contact Info

Product

Resources

About

BF-1 – A novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs

Cited by 20 publications

References 21 publications

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Ethenzamide Exerts Analgesic Effect at the Spinal Cord <i>via</i> Multiple Mechanisms of Action Including the 5HT<sub>2B</sub> Receptor Blockade in the Rat Formalin Test

Putative role of 5-HT2B receptors in migraine pathophysiology

Contact Info

Product

Resources

About

Putative role of 5-HT_2B receptors in migraine pathophysiology