5-HT receptors are a group of G protein-coupled receptors and ligand-gated ion channels in the central nervous system and peripheral nervous system. They mediate excitatory and inhibitory neurotransmission. Specifically, Serotonin receptors exist in almost all animals, and can even regulate the longevity and behavioral senescence of Caenorhabditis elegans. Besides, 5-HT plays a variety of roles by binding to cell surface receptors. Cell surface receptors are including seven different families (5-HT1 to 5-HT7). Moreover, the 5-HT receptor plays an important role in various neuropsychiatric diseases, such as anxiety, depression, schizophrenia, migraine, and drug addiction. Furthermore, the 5-HT receptor may also play an important role in obesity, aggressive behavior, sexual behavior, and cardiovascular disease.

In the digestive tract, stimulation of the 5-HT₄ receptor leads to a variety of effects, including promoting peristaltic reflex, guinea pig ileum, and so on. Meanwhile, the 5-HT₄ receptor has a wide distribution of tissue and is positively coupled with adenylate cyclase. In the brain, the 5-HT₄ receptor is located on neurons, many of which mediate the slow excitatory response to 5-HT. Nonetheless, 5-HT plays a physiological role in the regulation of gastrointestinal motility. Here, we will introduce a selective and competitive 5-HT₄ antagonist, SB-203186.

SB-203186 is a Selective and Competitive 5-HT₄ Antagonist.

Above all, SB-203186 antagonizes the 5-HT₄ receptor-mediated relaxations of the carbachol-contracted rat isolated oesophagus against 5-HT. Importantly, it has pK_B values of 10.9 (rat oesophagus), 9.5 (guinea-pig ileum), and 9.0 (human colon) respectively.

Next in importance, SB-203186 with 10 μM pretreatment enhances the 5-HT-induced contractions of the antral stripes. Particularly, intraduodenally administered SB-203186 with 0.3-3 mg/kg to newborn Camborough piglets produced blockade of 5-HT-evoked tachycardia. Obviously, this was maximal after 20 min and lasted for more than 3 h with 0.3 mg/kg. Interestingly, SB-203186 with 0.1-3 mg/kg by i.v. surmountable antagonised 5-HT-evoked tachycardia in anesthetized Yucatan minipigs or newborn Camborough piglets with similar potency.

Once more, SB-203186 enhanced 5-HT-induced contractions in the antrum. In addition, sb203186 increased gastric fundus contraction induced by 5-HT, suggesting that the 5-HT₄ receptor is involved in relaxation.

All in all, SB-203186 hydrochloride is a selective and competitive 5-HT₄ antagonist.

References:

S G Parker, et al. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):28-35.

Tohru Komada, et al. Biol Pharm Bull. 2007 Mar;30(3):508-13.