Chemical Modifications on 4-Arylpiperazine-Ethyl Carboxamide Derivatives Differentially Modulate Affinity for 5-HT1A, D4.2, and α2A Receptors: Synthesis and In Vitro Radioligand Binding Studies

2010 ◽  
Vol 63 (1) ◽  
pp. 56 ◽  
Author(s):  
Amaury Graulich ◽  
Marc Léonard ◽  
Mélissa Résimont ◽  
Xi-Ping Huang ◽  
Bryan L. Roth ◽  
...  
Keyword(s):  
Phenyl Ring ◽  
Radioligand Binding ◽  
Side Chain ◽  
Binding Studies ◽  
Chemical Modifications ◽  
Receptor Selectivity ◽  
Radioligand Binding Studies

A series of substituted 4-aryl-piperazine-ethyl heteroarylcarboxamides were prepared and tested in in vitro radioligand binding studies. The presence of a quinoxaline has a favourable impact in terms of serotonin 5-HT1A versus dopamine D4.2 receptor selectivity. Compounds with a 3-CF3 group at the distal phenyl ring are the most effective in terms of affinity and selectivity for 5-HT1A versus D4.2 receptors. A 4-phenyl-1,2,3,6-tetrahydropyridine in place of the corresponding 4-phenyl-piperazine side chain is also favourable not only for the affinity for 5-HT1A and D4.2 receptors but also in some cases for α 2A-adrenoceptors.

3'- and 4'-chloro-substituted analogs of benztropine: intravenous self-administration and in vitro radioligand binding studies in rhesus monkeys

2000 ◽  
Vol 147 (4) ◽  
pp. 426-435 ◽  
Author(s):  
W. L. Woolverton ◽  
J. K. Rowlett ◽  
K. M. Wilcox ◽  
I. A. Paul ◽  
R. H. Kline ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
Radioligand Binding ◽  
Self Administration ◽  
Binding Studies ◽  
Radioligand Binding Studies

Bronchospasmolytic and Adenosine Binding Activity of 8- (Proline / Pyrazole)-Substituted Xanthine Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Sneha Singh ◽  
Madhwi Ojha ◽  
Divya Yadav ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Radioligand Binding ◽  
Binding Activity ◽  
Receptor Subtypes ◽  
Significant Protection ◽  
Binding Studies ◽  
Standard Drug ◽  
Xanthine Derivatives ◽  
Radioligand Binding Studies ◽  
Micromolar Range

Background: ABSTRACT: Background: 8-Phenyltheophylline derivatives exhibit prophylactic effects at a specific dose but do not produce the cardiovascular or emetic side effects associated with xanthines, thereby exhibiting unique characteristics of potential therapeutic importance. Methods: Novel series of 8-(proline/pyrazole)-substituted xanthine analogs has been synthesized. The affinity and selectivity of compounds to adenosine receptors have been assessed by radioligand binding studies. The synthesized compounds also showed good bronchospasmolytic properties (increased onset of bronchospasm; decreased duration of jerks) with 100% survival of animals in comparison to the standard drug. Besides, compound 8f & 9f showed good binding affinity in comparison to other synthesized compounds in the micromolar range. Results: The maximum binding affinity of these compounds was observed for A2B receptors, which is ~ 7 or 10 times higher as compared to A1, A2A and A3 receptors. The newly synthesized derivatives 8f, 9a-f, 17g-m, and 18g-m displayed significant protection against histamine aerosol induced bronchospasm in guinea pigs. Conclusion: Newly synthesized proline/pyrazole based xanthines compounds showed a satisfactory binding affinity for adenosine receptor subtypes. Replacement or variation of substituted proline ring with substituted pyrazole scaffold at 8thposition of xanthine moiety resulted in the reduction of adenosine binding affinity and bronchospasmolytic effects.

Radioligand Binding Studies on the Nucleoside Transport Protein

1991 ◽  
pp. 411-414
Author(s):  
Ad P. Ijzerman ◽  
Armand Voorschuur ◽  
Marieke Kruidering ◽  
Irene M. Pirovano ◽  
Herman Van Belle ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Transport Protein ◽  
Nucleoside Transport ◽  
Binding Studies ◽  
Radioligand Binding Studies

Endothelium-independent vascular relaxation mediating ETB receptor in rabbit mesenteric arteries

1999 ◽  
Vol 276 (2) ◽  
pp. H383-H390 ◽  
Author(s):  
Takanori Iwasaki ◽  
Mitsuru Notoya ◽  
Yoko Hayasaki-Kajiwara ◽  
Toshitake Shimamura ◽  
Noriyuki Naya ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Radioligand Binding ◽  
Muscle Layer ◽  
Mesenteric Arteries ◽  
Binding Studies ◽  
Camp Content ◽  
Rabbit Mesenteric Artery ◽  
Etb Receptor ◽  
Radioligand Binding Studies ◽  
Rabbit Mesenteric Arteries

Vascular response mediating endothelin (ET)Breceptor was studied using isolated rabbit mesenteric arteries. ET-1 (0.1–30 nM) caused a concentration-dependent contraction, whereas ET-3 >100 nM caused only weak contraction. Up to 1 μM of sarafotoxin S6c showed no contraction. In arteries precontracted with phenylephrine, ET-3 (0.03–1 nM) caused a concentration-dependent relaxation, which was not affected by endothelium denudation. The ET-3-induced relaxation was antagonized by BQ-788 and PD-142893 but not by BQ-123 in the endothelium-denuded arteries. Treatment with indomethacin but not with N G-nitro-l-arginine methyl ester completely inhibited the relaxation. ET-3 stimulated the release of 6-keto-PGF1α and PGE2 from the endothelium-denuded arteries. ET-3 also significantly increased cAMP content but not cGMP content in the arteries. Radioligand-binding studies using serial sections of the artery revealed the expression of not only ETA but also ETB receptors in the smooth muscle layer of the arteries. These results suggest that ET-3 activates ETB receptor in smooth muscle cells of rabbit mesenteric artery, producing vasodilator prostaglandins from arachidonic acid probably via a catalysis of cyclooxygenase, which accumulates cAMP in subendothelial tissues and produces relaxations.

Synthesis and radioligand binding studies of bis-(8-isopropyl-isoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels

2011 ◽  
Vol 21 (22) ◽  
pp. 6756-6759 ◽  
Author(s):  
Eduard Badarau ◽  
Sébastien Dilly ◽  
Fabien Dufour ◽  
Sylvie Poncin ◽  
Vincent Seutin ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Binding Studies ◽  
Radioligand Binding Studies
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