scholarly journals Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: Effect of the N-5 bond type on the affinity and selectivity at the four adenosine receptor subtypes

2007 ◽  
Vol 4 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Chiara Bolcato ◽  
Claudia Cusan ◽  
Giorgia Pastorin ◽  
Giampiero Spalluto ◽  
Barbara Cacciari ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Receptor Subtypes ◽  
Receptor Antagonists ◽  
Bond Type

Receptors subtypes involved in adenosine-mediated modulation of norepinephrine release from cardiac nerve terminals

2004 ◽  
Vol 82 (11) ◽  
pp. 1026-1031 ◽  
Author(s):  
Mojca Lorbar ◽  
Eugene S Chung ◽  
Arash Nabi ◽  
Katarina Skalova ◽  
Richard A Fenton ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Stellate Ganglion ◽  
Receptor Subtypes ◽  
Nerve Terminals ◽  
Norepinephrine Release ◽  
Receptor Antagonists ◽  
Cardiac Nerve ◽  
Mediated Effects ◽  
Discernible Effect ◽  
Rat Hearts

The objective of this study was to determine which adenosine receptor subtypes were involved in the modulation of norepinephrine release from cardiac nerve terminals. In addition, the persistence of adenosine-mediated effects was evaluated. Rat hearts attached to the stellate ganglion were isolated and perfused. The ganglion was electrically stimulated twice (S1 and S2), allowing 10 min between the stimulations. To determine adenosine receptor subtypes, selective and nonselective adenosine agonists and antagonists were infused following S1 and until the end of S2. To evaluate the persistence of adenosine-mediated effect on norepinephrine release, the stellate ganglion was stimulated a third (S3) and fourth (S4) time. Coronary effluents were collected to determine norepinephrine content. Adenosine and a selective A1 receptor agonist, CCPA, inhibited norepinephrine release by 49% and 54%, respectively. This effect was reversed by simultaneous infusion of nonspecific (8-SPT) and specific (DPCPX) A1 receptor antagonists. Selective A2A (CGS 21680) and A3 (AB-MECA) receptor agonists had no discernible effect on norepinephrine release. Similarly, adenosine A2A receptor antagonists CSC and DMPX did not alter the dose-response relation between norepinephrine release and adenosine. Finally, the inhibitory effects of adenosine on norepinephrine release did not persist 10 min subsequent to the removal of adenosine. Adenosine inhibited norepinephrine release primarily via the adenosine A1 receptor. This effect of adenosine was of short duration. Adenosine A2A and A3 receptors were either absent or functionally insignificant in the regulation of norepinephrine release in the rat heart.Key words: adenosine, norepinephrine, receptor, rat, neurotransmitters.

scholarly journals Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Siew Lee Cheong ◽  
Gopalakrishnan Venkatesan ◽  
Priyankar Paira ◽  
Ramasamy Jothibasu ◽  
Alexander Laurence Mandel ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Rational Design ◽  
Receptor Subtypes ◽  
Receptor Antagonists ◽  
Design And Optimization ◽  
The Past ◽  
Chemistry Research ◽  
Pathological Conditions ◽  
Structure Activity ◽  
Selective Antagonists

In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3) has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR) profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.

Pyrazolo-Triazolo-Pyrimidine Derivatives as Adenosine Receptor Antagonists: A Possible Template for Adenosine Receptor Subtypes?

2002 ◽  
Vol 8 (26) ◽  
pp. 2299-2332 ◽  
Author(s):  
Pier Baraldi ◽  
Barbara Cacciari ◽  
Pier Borea ◽  
Katia Varani ◽  
Giorgia Pastorin ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Receptor Subtypes ◽  
Pyrimidine Derivatives ◽  
Receptor Antagonists

Ligand-Based Virtual Screening Using Tailored Ensembles: A Prioritization Tool for Dual A2A Adenosine Receptor Antagonists / Monoamine Oxidase B Inhibitors

2016 ◽  
Vol 22 (21) ◽  
pp. 3082-3096 ◽  
Author(s):  
Aliuska Morales Helguera ◽  
Yunierkis Perez-Castillo ◽  
M. Natália D.S. Cordeiro ◽  
Eduardo Tejera ◽  
César Paz-y-Miño ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Monoamine Oxidase ◽  
Adenosine Receptor ◽  
Monoamine Oxidase B ◽  
Receptor Antagonists ◽  
A2a Adenosine Receptor

Comparative pharmacology of human adenosine receptor subtypes – characterization of stably transfected receptors in CHO cells

1997 ◽  
Vol 357 (1) ◽  
pp. 1-9 ◽  
Author(s):  
K.-N. Klotz ◽  
J. Hessling ◽  
J. Hegler ◽  
C. Owman ◽  
B. Kull ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Cho Cells ◽  
Receptor Subtypes

scholarly journals Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

2013 ◽  
Vol 82 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Organ Bath ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

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