Novel serotonin receptor 2 (5-HT₂R) agonists and antagonists: a patent review (2004-2014)

Abstract

Introduction: Serotonin or 5-hydroxytryptamine (5-HT) is a substance found in plasma, which increases smooth muscle contraction and mediates platelet aggregation. In addition, it is a monoamine neurotransmitter and is implicated in diverse behaviors. The serotonin receptor 2 (5-HT₂) subfamily is best known for biased signaling and is strongly expressed mainly in the brain regions postulated to be involved in the modulation of higher cognitive and affective functions. Modulators of the 5-HT₂ receptor are currently used to treat a variety of diseases including chronic pain and psychonosema. These properties suggest that 5-HT₂ receptors may become an important therapeutic target for the treatment of various pathological conditions.

Areas covered: This review highlights the significant progress that has been made in the discovery and development of 5-HT₂ receptor agonists and antagonists based on an analysis of the patent literature between January 2004 and December 2014.

Expert opinion: Cumulative evidence over the past decade supports the notion that the modulation of 5-HT₂ receptors has a positive effect on human cognition and emotion. Therefore, we suggest that new agonists and antagonists may play an important role in the treatment of disorders such as schizophrenia, addiction and obesity.

Keywords:

• agonists
• antagonists
• biased signaling
• mental disorders
• serotonin receptor 2

Article highlights

• This review focused on and highlighted compounds with data that indicate excellent 5-HT_2A, 5-HT_2B and 5-HT_2C receptor subtype selectivity.

• The modulation of each subtype of the 5-HT receptor results in both overlapping and nonintersecting disparities in physiological effects.

• The development of selective agonists and antagonists at 5-HT₂ receptor subtypes will greatly facilitate the investigation of signal transduction pathways mediated by a signal receptor subtype. Furthermore, highly selective and exquisite ligands will act as powerful tools to enhance the evaluation and deciphering of conformational alterations in 5-HT₂ receptor-related biased signaling.

• However, it should be noted that nonselective ligands could be an advantageous solution to the dilemma of therapeutic adverse and side effects.

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