The adrenergic receptor antagonist carvedilol interacts with serotonin 2A receptors both in vitro and in vivo

Publication date: Available online 15 April 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): Kevin Sean Murnane, Osman F. Guner, J. Phillip Bowen, Kalyn M. Rambacher, Nader H. Moniri, Tyler J. Murphy, Cedrick Maceo Daphney, Aboagyewaah Oppong-Damoah, Kenner C. RiceAbstractThere is increasing support for the potential clinical use of compounds that interact with serotonin 2A (5-HT2A) receptors. It is therefore of interest to discover novel compounds that interact with 5-HT2A receptors. In the present study, we used computational chemistry to identify critical ligand structural features of 5-HT2A receptor binding and function. Query of compound databases using those ligand features revealed the adrenergic receptor antagonist carvedilol as a high priority match. As carvedilol is used clinically for cardiovascular diseases, we conducted experiments to assess whether it has any interactions with 5-HT2A receptors. In vitro experiments demonstrated that carvedilol has high nanomolar affinity for 5-HT2A receptors. In vivo experiments demonstrated that carvedilol increases the ethanol-induced loss of the righting reflex and suppresses operant responding in mice, and that these effects are attenuated by pretreatment with the selective 5-HT2A receptor antagonist M100907. Moreover, carvedilol did not induce the head-twitch response in mice, suggesting a lack of psychedelic effects. However, carvedilol did not activate canonical 5-HT2A receptor signaling pathways and antagoniz...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research