We Need 2C but Not 2B: Developing Serotonin 2C (5‐HT<sub>2C</sub>) Receptor Agonists for the Treatment of CNS Disorders

Cheng, Jianjun; Kozikowski, Alan P.

doi:10.1002/cmdc.201500437

Cited by 18 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RNA editing generates at least 14 functionally distinct 5-HTR2C isoforms, any of which could be a potential target for improved therapeutic and side effect profiles [ 90 ]. Moreover, the negligible presence of 5-HTR2C in cardiac and vascular tissues makes these receptors ideal targets for treatment of brain disorders, due to their limited peripheral side effects [ 91 ].…”

Section: Serotonin Receptors (5-htr)mentioning

confidence: 99%

The serotonergic system and cognitive function

Štrac

Pivac

Mück‐Šeler

2016

Translational Neuroscience

194

108

View full text Add to dashboard Cite

Symptoms of cognitive dysfunction like memory loss, poor concentration, impaired learning and executive functions are characteristic features of both schizophrenia and Alzheimer’s disease (AD). The neurobiological mechanisms underlying cognition in healthy subjects and neuropsychiatric patients are not completely understood. Studies have focused on serotonin (5-hydroxytryptamine, 5-HT) as one of the possible cognitionrelated biomarkers. The aim of this review is to provide a summary of the current literature on the role of the serotonergic (5-HTergic) system in cognitive function, particularly in AD and schizophrenia.The role of the 5-HTergic system in cognition is modulated by the activity and function of 5-HT receptors (5-HTR) classified into seven groups, which differ in structure, action, and localization. Many 5-HTR are located in the regions linked to various cognitive processes. Preclinical studies using animal models of learning and memory, as well as clinical in vivo (neuroimaging) and in vitro (post-mortem) studies in humans have shown that alterations in 5-HTR activity influence cognitive performance.The current evidence implies that reduced 5-HT neurotransmission negatively influences cognitive functions and that normalization of 5-HT activity may have beneficial effects, suggesting that 5-HT and 5-HTR represent important pharmacological targets for cognition enhancement and restoration of impaired cognitive performance in neuropsychiatric disorders.

show abstract

Section: Serotonin Receptors (5-htr)mentioning

confidence: 99%

The serotonergic system and cognitive function

Štrac

Pivac

Mück‐Šeler

2016

Translational Neuroscience

194

108

View full text Add to dashboard Cite

show abstract

“…The 5-HT 2C receptor represents a promising drug target for obesity and central nervous system disorders, such as schizophrenia and drug addiction [1e4]. Subtype selectivity is essential for the development of potential 5-HT 2C -targeted therapeutics [5], as drugs with 5-HT 2B agonism may induce potentially life-threatening valvular hypertrophy [6,7], while 5-HT 2A agonists are hallucinogenic [8]. However, it is currently a major challenge to develop agonists that are highly selective for 5-HT 2C over 5-HT 2B and 5-HT 2A due to these subtypes' significant homology at structural, genetic, and functional levels.…”

Section: Introductionmentioning

confidence: 99%

Design of fluorinated cyclopropane derivatives of 2-phenylcyclopropylmethylamine leading to identification of a selective serotonin 2C (5-HT2C) receptor agonist without 5-HT2B agonism

Zhang

McCorvy

Shen

et al. 2019

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

A new series of fluorinated 5-HT 2C agonists were designed and synthesized on the basis of our previous work on 2-phenylcyclopropylmethylamines as a potential approach for the treatment of central nervous system disorders. Key fluorinated cyclopropane moieties were constructed through transition metal catalyzed [2 þ 1]-cycloaddition of aromatic vinyl fluorides, and the absolute stereochemistry of the representative compound (e)-21a was established. Functional activity measuring calcium flux at 5-HT 2 receptors reveals high potency for compounds (þ)-21a-d. In particular, (þ)-21b had no detectable 5-HT 2B agonism and displayed reasonable selectivity against 5-HT 2A. Molecular docking studies were further performed to explain the compounds' possible binding poses to the 5-HT 2C receptor.

show abstract

“…Further studies have shown that dopamine is preferred and favored as the first line of medication as it increases the arterial pressure mainly through vasoconstriction having little effect on the cardiac output, stroke volume, and the heart rate [29]. Studies carried out have shown that the use of dopamine increases the stroke volume and heart rate.…”

Section: Discussionmentioning

confidence: 99%

Comparing the Use of Dopamine and Norepinephrine in Shock Treatment

Jalalyazdi¹,

Parvizian²,

Abyaneh³

2016

Cardiovasc Pharm Open Access

View full text Add to dashboard Cite

IntroductionCardiovascular shock refers to a critical condition that occurs when a patient's heart suddenly fails to pump blood as required by the body. This rare but fatal condition is mostly caused by heart attack and is linked to high death rate [1,2]. The fluid administration that forms the firstline of therapeutic strategy does not offer enough stability for the condition of the patient, and the adrenergic agents are regularly needed to correct hypertension [3]. Among the most frequently used agents are dopamine and norepinephrine. Both dopamine and norepinephrine affect the alpha-adrenergic and beta-adrenergic receptors, though to varying degrees. The effects of alpha-adrenergic receptors lead to increased vascular tone. However, it could decrease the cardiac output as well as the regional flow of blood, particularly in cutaneous, renal, and splanchnic beds [4].On the other hand, beta-adrenergic effects assist in the maintenance of blood flow through inotropic and chronotropic effects as well as increasing splanchnic perfusion. This stimulation from the betaadrenergic effects can bring out the unwanted consequences, including an increase in the cellular metabolism and immunosuppressive effects [5]. Besides, dopamine arouses dopaminergic receptors, which leads to a uniformly bigger rise in renal and splanchnic perfusion, which can expedite lung edema tenacity. Conversely, the stimulation caused by dopamine could lead to negative immunological effects by modifying hypothalamic-pituitary function, leading to a patent drop of prolactin as well as the level of hormones [6].Hypothetically, norepinephrine and dopamine have varying effects in the splanchnic, kidney and pituitary axis, though the medical consequences of the implied differences are not certain [7]. Experts have recommended that any of the two compounds may be chosen first and applied as a vasopressor in patients suffering from shock. Studies have Comparing the Use of Dopamine and Norepinephrine in Shock Treatment AbstractBackground: The vasopressor agents, such as norepinephrine and dopamine have been endorsed as the standard choice for shock treatment. However, there is controversy regarding the use of vasopressor agents for shock treatment. Considering the use of norepinephrine over dopamine, the present study aimed at assessing the reasons for the reduced death rate among the patients who were in shock.

show abstract

We Need 2C but Not 2B: Developing Serotonin 2C (5‐HT_2C) Receptor Agonists for the Treatment of CNS Disorders

Cited by 18 publications

References 44 publications

The serotonergic system and cognitive function

The serotonergic system and cognitive function

Design of fluorinated cyclopropane derivatives of 2-phenylcyclopropylmethylamine leading to identification of a selective serotonin 2C (5-HT2C) receptor agonist without 5-HT2B agonism

Comparing the Use of Dopamine and Norepinephrine in Shock Treatment

Contact Info

Product

Resources

About

We Need 2C but Not 2B: Developing Serotonin 2C (5‐HT2C) Receptor Agonists for the Treatment of CNS Disorders

Cited by 18 publications

References 44 publications

The serotonergic system and cognitive function

The serotonergic system and cognitive function

Design of fluorinated cyclopropane derivatives of 2-phenylcyclopropylmethylamine leading to identification of a selective serotonin 2C (5-HT2C) receptor agonist without 5-HT2B agonism

Comparing the Use of Dopamine and Norepinephrine in Shock Treatment

Contact Info

Product

Resources

About

We Need 2C but Not 2B: Developing Serotonin 2C (5‐HT_2C) Receptor Agonists for the Treatment of CNS Disorders