Sarpogrelate Dilates Cerebral Arteries in the Absence of Exogenous Serotonin

Pharmacology & Therapeutics

Ayme-Dietrich

Aubertin-Kirch

et al. 2017

Serotonergic dysfunction is mainly associated with neuropsychiatric and cardiovascular disorders but has also been linked with many other pathological conditions. Serotonin (5-hydroxytryptamine, 5-HT) mediates numerous physiological functions in the brain and the periphery by activating a variety of receptors. 5-HT receptors are divided into four classes, three of which belong to the G protein-coupled receptor family. This review provides an overview of the recent pharmacological developments involving the Gq-coupled 5-HT receptor subfamily as well as the pathological implications of this receptor subfamily with regard to fibrosis, the central nervous system, cardiovascular disorders, and cancer. The final section highlights new therapeutic opportunities and emerging research revealing unexplored medical opportunities for this class of 5-HT receptors. The development of biased 5-HT receptor ligands appears to be an interesting topic in various areas. In light of recent discoveries, the need for the development of new and safer drugs should take into account the risk of cardiovascular side effects such as pulmonary hypertension and heart valve disease.

Section: Vascular Tone Of Systemic and Coronary Arteriesmentioning

confidence: 91%

New therapeutic opportunities for 5-HT2 receptor ligands

Pharmacology & Therapeutics

Ayme-Dietrich

Aubertin-Kirch

et al. 2017

“…In humans, sarpogrelate given as a single 200 mg oral administration also increased basal and maximal (adenosine triphosphate) average peak velocity of coronary blood flow in patients with coronary artery disease. Such a vasodilatation was also observed in rabbit cerebral arteries (Kawamura, et al, 2013) and experimental vein grafts (Kodama, et al, 2009). Mechanisms of sarpogrelate effects are not fully understood.…”

Section: Coronaropathy and Ischemic Preconditioningmentioning

confidence: 90%

Serotonin and Cardiovascular Diseases

Monassier

2019

Serotonin

Serotonergic dysfunction is mainly associated with neuropsychiatric and cardiovascular disorders but has also been linked with many other pathological conditions. This review provides an overview of the recent pharmacological developments involving 5hydroxytryptamine (5-HT; serotonin), released from blood platelets, in the human cardiovascular system. The acute cardiovascular response to serotonin, named the Bezold-Jarish reflex, leads to intense bradycardia associated with atrioventricular block, and involves 5-HT 3 , 5-HT 1B , 5-HT 7 and 5-HT 2A/2B receptors. The contribution of serotonin and its receptors (5-HT 4 and 5-HT 2A/2B ) in cardiac development, in cardiovascular tissue remodeling, with a particular emphasis on cardiac hypertrophy, fibrosis and failure, in valve degeneration, is explored in this review. Some new aspects of 5-HT 1B , 5-HT 7 and 5-HT 2A/2B receptors in vasomotor tone regulation and the interaction between endothelial and smooth muscle cells are also be discussed. As well, serotonin, its transporter, 5-HT 1B , and 5-HT 2B receptors participation in pulmonary hypertension and pulmonary vascular remodeling are presented. Finally, the contribution of bone marrow derived endothelial progenitors in the pathogenesis of pulmonary hypertension and interactions with bone morphogenic protein type 2 receptor signaling are highlighted. The aim of this review is thus to emphasize the vascular, cardiac and pulmonary effects caused by serotonin receptor activation, and to highlight their possible prevention by the development of new drugs targeting this system.

Cardiovascular remodeling and the peripheral serotonergic system

Ayme-Dietrich¹,

Aubertin-Kirch²,

Archives of Cardiovascular Diseases

et al. 2017

Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, plays a major role in the human cardiovascular system. Besides the effect of endogenous serotonin, many drugs targeting serotonergic receptors are widely used in the general population (antiobesity agents, antidepressants, antipsychotics, antimigraine agents), and may enhance the cardiovascular risk. Depending on the type of serotonin receptor activated and its location, the use of these compounds triggers acute and chronic effects. The acute cardiovascular response to 5-HT, named the Bezold-Jarish reflex, leads to intense bradycardia associated with atrioventricular block, and involves 5-HT, 5-HT, 5-HT and 5-HT receptors. The chronic contribution of 5-HT and its receptors (5-HT and 5-HT) in cardiovascular tissue remodeling, with a particular emphasis on cardiac hypertrophy, fibrosis and valve degeneration, will be explored in this review. Finally, through the analysis of the effects of sarpogrelate, some new aspects of 5-HT receptor pharmacology in vasomotor tone regulation and the interaction between endothelial and smooth muscle cells will also be discussed. The aim of this review is to emphasize the cardiac side effects caused by serotonin receptor activation, and to highlight their possible prevention by the development of new drugs targeting this system.