Related Experiment Video
Updated: Jan 31, 2026
Platelet Adhesion and Aggregation Under Flow using Microfluidic Flow Cells
Published on: October 27, 2009
Anti-aggregation effect on platelets of Indiplon a hypnotic sedative non-benzodiazepine drug
C F Burgos1, C Sanchéz2, C Sepúlveda3
1Department of Physiology, Faculty of Biological Sciences, Universidad de Concepción, Chile.
Insights
Indiplon, an insomnia drug, acts as an adenosine A2A receptor agonist. It inhibits platelet aggregation and activation, suggesting a potential role in cardiovascular protection.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Platelet Biology
Background:
- Cardiovascular diseases are a major public health concern.
- Platelet activity alterations are central to many cardiovascular disease pathologies.
- Platelet activation is regulated by intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP).
Purpose of the Study:
- To investigate the potential of Indiplon, an insomnia medication, to activate adenosine A2A receptors.
- To analyze the effects of Indiplon on platelet activity in vitro.
- To explore Indiplon's potential cardiovascular protective role through platelet modulation.
Main Methods:
- In silico molecular docking to assess Indiplon's binding affinity to the adenosine A2A receptor.
- In vitro functional assays using platelet-rich plasma (PRP) to measure platelet aggregation.
- Assessment of P-selectin expression on platelet membranes.
Main Results:
- Indiplon demonstrated significant binding to the adenosine A2A receptor in silico (ΔGbind of -73.321 kcal/mol).
- Indiplon (500 μM) inhibited ADP-induced platelet aggregation by 70% in PRP.
- A2A receptor antagonists (ZM241385, MSX-2) partially blocked Indiplon's inhibitory effect on platelet aggregation.
- Indiplon reduced P-selectin expression, indicating decreased platelet activation.
Conclusions:
- Indiplon functions as an adenosine A2A receptor agonist.
- Activation of A2A receptors by Indiplon inhibits platelet aggregation and activation.
- Indiplon exhibits potential cardiovascular protective effects mediated by platelet modulation.
Abstract:
Cardiovascular diseases are one of the main public health problems, and many of them, their pathophysiology involves alterations in platelet activity. Platelet activation is an essential event that is regulated by the intracellular concentrations of Ca2+ and cAMP. Interestingly, it has been shown that the activation of adenosine A2A receptors increases cAMP levels and produces the inhibition of platelet aggregation, which appears as a potential target for regulation of platelet activity. Therefore, we tried to activate A2A receptors using Indiplon, a drug developed for the treatment of insomnia, and analyze its effect on platelet activity in vitro. Our results indicate that Indiplon is able to interact in silico with the adenosine A2A receptor (ΔGbind of -73.321 kcal/mol, similar to that obtained with adenosine), which is involved in the regulation of platelet cAMP levels. In functional studies using PRP, a reduction in platelet aggregation induced by ADP was observed in the presence of Indiplon at 500 μM with a percentage of inhibition 70%, where the use of specific inhibitors (ZM241385 and MSX-2) of the A2A receptor also blocked these effects reducing the percentage of inhibition to 41% and 34.1%, respectively. Also, the use of Indiplon produced a decrease in the expression in the membrane of P-selectin. Thus, Indiplon acts as an A2A receptor agonist and whose activation results in inhibition of platelet aggregation and activation, showing a possible cardiovascular protective role.
More Related Videos
09:13Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
05:49Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
Related Concept Videos
01:19Sedatives and Hypnotics Drugs: Benzodiazepines
Benzodiazepines work by enhancing the effects of the inhibitory neurotransmitter GABA. They bind to the GABAA receptor, increasing its affinity for GABA, which opens chloride...
01:20Sedatives and Hypnotics Drugs: Barbiturates
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
01:23Sedatives and Hypnotics: Overview
Sedative-hypnotics are categorized into barbiturates, benzodiazepines (BZDs), and non-benzodiazepines or Z-drugs. These drugs work by suppressing central nervous system activity, and this suppression is dose-dependent. Older sedative medications, like barbiturates, follow a linear curve in...
01:29Anxiolytic Drugs: Benzodiazepines and Buspirone
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...