"Selective" Serotonin 5-HT Receptor Antagonists

Overview

Journal Biochem Pharmacol

Specialties Biochemistry
Pharmacology

Date 2022 Apr 5

PMID 35381208

Authors

Austen B Casey

Meng Cui

Raymond G Booth

Clinton E Canal

Affiliations

Soon will be listed here.

Abstract

Blockade of the serotonin 5-HT G protein-coupled receptor (5-HTR) is a fundamental pharmacological characteristic of numerous antipsychotic medications, which are FDA-approved to treat schizophrenia, bipolar disorder, and as adjunctive therapies in major depressive disorder. Meanwhile, activation of the 5-HTR by serotonergic psychedelics may be useful in treating neuropsychiatric indications, including major depressive and substance use disorders. Serotonergic psychedelics and other 5-HTR agonists, however, often bind other receptors, and standard 5-HTR antagonists lack sufficient selectivity to make well-founded mechanistic conclusions about the 5-HTR-dependent effects of these compounds and the general neurobiological function of 5-HTRs. This review discusses the limitations and strengths of currently available "selective" 5-HTR antagonists, the molecular determinants of antagonist selectivity at 5-HTRs, and the utility of molecular pharmacology and computational methods in guiding the discovery of novel unambiguously selective 5-HTR antagonists.

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