In vitro and in vivo pharmacological characterisation of the potent and selective vasopressin V1A receptor antagonist 4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl-(3,5-difluoro-phenyl) methanone (PF-00738245)

2011 ◽  
Vol 670 (2-3) ◽  
pp. 347-355 ◽  
Author(s):  
Rachel Russell ◽  
Rachel Doyle ◽  
Jamie Turner ◽  
Neil Attkins ◽  
Simeon Ramsey ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
V1a Receptor ◽  
Vasopressin V1a Receptor

Potent Inhibitory Effect of Sr 49059, An Orally Active Non-Peptide Vasopressin via Receptor Antagonist, on Human Arterial Coronary Bypass Graft

1995 ◽  
Vol 89 (5) ◽  
pp. 481-485 ◽  
Author(s):  
James J. Liu ◽  
Joan R. Chen ◽  
Brian B. Buxton ◽  
Colin I. Johnston ◽  
Louise M. Burrell
Keyword(s):  
Receptor Antagonist ◽  
Bypass Graft ◽  
Coronary Bypass ◽  
Inhibitory Effect ◽  
V1a Receptor ◽  
Mammary Arteries ◽  
Coronary Bypass Graft ◽  
Internal Mammary ◽  
Vasopressin V1a Receptor

1. The effect of vasopressin receptor antagonists varies between analogues (peptide, non-peptide) and across species. In this study the effect of the novel non-peptide vasopressin V1a receptor antagonist SR 49059 on human internal mammary arteries was investigated. 2. SR 49059 produced a potent, concentration-dependent, inhibitory effect on vasopressin-induced contraction of human coronary bypass graft internal mammary arteries. Both SR 49059 (1 μmol/l) and a peptide selective V1a antagonist {[d(CH2)5sarcosine7]arginine vasopressin} (1 μmol/l) abolished vasopressin-induced contraction. The non-peptide V1a receptor antagonist OPC-21268 (1 μmol/l) had no effect on vasopressin-induced contraction. 3. The effect of SR 49059 was specific to vascular vasopressin receptors as noradrenaline-induced contraction was not influenced by SR 49059. 4. The results of this study in vitro indicate that the non-peptide SR 49059 is a potent, specific vasopressin V1a receptor antagonist in the human internal mammary artery and suggest that it may be a useful tool for studying the pathophysiological role of vasopressin in man.

scholarly journals Synthesis, in vitro and in vivo evaluation of 11C-O-methylated arylpiperazines as potential serotonin 1A (5-HT1A) receptor antagonist radiotracers

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Vidya Narayanaswami ◽  
Junchao Tong ◽  
Ferdinando Fiorino ◽  
Beatrice Severino ◽  
Rosa Sparaco ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
In Vivo Evaluation

Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: Possible confounding effects on in vivo and in vitro studies

2012 ◽  
Vol 22 (21) ◽  
pp. 6661-6664 ◽  
Author(s):  
Charles J. McElhinny ◽  
Anita H. Lewin ◽  
S. Wayne Mascarella ◽  
Scott Runyon ◽  
Lawrence Brieaddy ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
In Vitro Studies

scholarly journals Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M2 and M3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

2017 ◽  
Vol 43 (5) ◽  
pp. 1790-1802 ◽  
Author(s):  
Hyun Jung Kim ◽  
Taewon Han ◽  
Yun Tai Kim ◽  
Insuk So ◽  
Byung Joo Kim
Keyword(s):  
Receptor Antagonist ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Potential ◽  
Pacemaker Potentials ◽  
Magnolia Officinalis ◽  
Cells Of Cajal ◽  
Gi Motility

Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.

Luteolin, a Potent Human Monoamine Oxidase-A Inhibitor and Dopamine D4 and Vasopressin V1A Receptor Antagonist

2020 ◽  
Vol 68 (39) ◽  
pp. 10719-10729
Author(s):  
Se Eun Park ◽  
Pradeep Paudel ◽  
Aditi Wagle ◽  
Su Hui Seong ◽  
Hyeong Rak Kim ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Receptor Antagonist ◽  
Monoamine Oxidase A ◽  
V1a Receptor ◽  
Vasopressin V1a Receptor

scholarly journals Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam J. Davenport ◽  
Ioana Neagoe ◽  
Nico Bräuer ◽  
Markus Koch ◽  
Andrea Rotgeri ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Underlying Disease ◽  
Nerve Fibers ◽  
P2x3 Receptor ◽  
P2x3 Receptors ◽  
Pain Pathways ◽  
Pathological Pain ◽  
Target Effects

AbstractATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved in pathways triggering cough and may contribute to the pathophysiology of endometriosis and overactive bladder. However, despite the strong therapeutic rationale for targeting P2X3 receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer. Here we present a P2X3 receptor antagonist, eliapixant (BAY 1817080), which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3. We show that eliapixant reduces inflammatory pain in relevant animal models. We also provide the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation, a phenomenon hypothesised to contribute to several diseases, including endometriosis. To test whether eliapixant could help treat endometriosis, we confirmed P2X3 expression on nerve fibers innervating human endometriotic lesions. We then demonstrate that eliapixant reduces vaginal hyperalgesia in an animal model of endometriosis-associated dyspareunia, even beyond treatment cessation. Our findings indicate that P2X3 antagonism could alleviate pain, including non-menstrual pelvic pain, and modify the underlying disease pathophysiology in women with endometriosis. Eliapixant is currently under clinical development for the treatment of disorders associated with hypersensitive nerve fibers.

scholarly journals Evidence of early vasogenic edema following minor head impact that can be reduced with a vasopressin V1a receptor antagonist

2020 ◽  
Vol 165 ◽  
pp. 218-227
Author(s):  
Praveen Kulkarni ◽  
Mansi R. Bhosle ◽  
Shi-fang Lu ◽  
Neal S Simon ◽  
Sade Iriah ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Vasogenic Edema ◽  
Head Impact ◽  
V1a Receptor ◽  
Vasopressin V1a Receptor
Sign in / Sign up

Export Citation Format

Share Document