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.

Thymosthenic Agents, A Novel Approach in the Treatment of Schizophrenia

1989 ◽  
Vol 155 (S5) ◽  
pp. 33-36 ◽  
Author(s):  
Yves G. Gelders
Keyword(s):  
Binding Sites ◽  
Psychotic Disorders ◽  
Radioligand Binding ◽  
Receptor Subtypes ◽  
Binding Studies ◽  
Novel Approach ◽  
Definition Of ◽  
Radioligand Binding Studies ◽  
Β Adrenergic Receptors ◽  
The Brain

The pharmacotherapy of psychotic disorders which started in 1952, based on empirical results obtained with chlorpromazine by Delay & Deniker, has revolutionised the treatment of psychiatric diseases of non-organic origin. The discovery of haloperidol by Janssen in 1959 represented further progress in this field, since this was found to be more potent and to have generally less disturbing adverse effects than chlorpromazine. Nevertheless it took several years before dopamine-antagonism was put forward as possible mechanism of action for neuroleptic drugs (Carlsson & Lindqvist, 1963). From the early 1970s, however, the advent of radioligand binding studies provided new tools for studying neurotransmitter receptors in the brain and for investigating the interaction of drugs with various receptors. This technique allowed identification of receptor-binding sites related to pharmacologically defined receptors and receptor subtypes, e.g. α and β-adrenergic receptors. It also led to further subclassification and refined definition of receptors, e.g. dopamine-D1 and -D2, and different pharmacological effects mediated by the receptor subtypes have been identified.

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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