By Jose M. Palacios, Angel Pazos, Daniel Hoyer (auth.), Giuseppe Di Giovanni, Ennio Esposito, Vincenzo Di Matteo (eds.)
Research of 5-HT2c receptors stretches again twenty-five years, and whereas a lot of it's been efficient, the prior decade of analysis has been notable by way of either volume produced and insights received. it's infrequently incredible that 5-HT2c receptor study has grown so fruitful, on condition that it's a well known imperative serotonin receptor subtype commonly expressed in the valuable and the peripheral frightened method and is believed to play a massive position within the rules of various behaviors. It has extra been proven by means of experimental and medical statement that it will probably signify a potential healing objective for the improvement of substances for various principal worried approach problems. The time, for this reason, is greater than applicable to provide the 1st ever assessment of the examine of 5-HT2c receptors. a part of the preferred and critical sequence, “The Receptors,” The 5-HT2c Receptor offers a radical replace of the sensible prestige of the 5-HT2c receptor. It covers the molecular, mobile, anatomical, biochemical and behavioral elements of this receptor on the way to spotlight its detailed regulatory homes and the rising sensible value of constitutive job and RNA-editing in vivo. additionally, the publication investigates the receptors’ healing power in various diversified illnesses, handled separately in separate chapters, together with melancholy, drug abuse, schizophrenia, consuming issues, Parkinson’s ailment, Prader-Willi Syndrome, Alzheimer’s sickness and epilepsy. whereas now not exhaustive, this article is an important software in realizing the earlier and encouraging the way forward for interdisciplinary learn at the 5-HT2c receptor.
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Extra info for 5-HT2C Receptors in the Pathophysiology of CNS Disease
1997b). 6, Structure II) displayed acceptable agonistic properties at 5-HT2C receptors (13 nmol/L < EC50 < 162 nmol/L). Of the two enantiomers of 55 (Structure II, R = 7-Cl) the R- was more potent than the S- (EC50 = 3 and 161 nmol/L, respectively). The introduction of a CH3 group in 4-position of the Structure II (Fig. 6) generated an additional chiral centre. The new compounds have two stereogenic centers and a maximum of four enantiomers. 4). Compound 56 (stereochemistry 4R,10aR) acted as full agonist with the highest affinity for all 5-HT2 receptors.
Modeling studies of 23 showed an almost orthogonal relationship between the two aryl rings. However, this group of compounds yet displayed poor oral activity or inhibitory activity of other P450 enzymes. 2, R3 = 3-Py, R4 = R5 = H) was studied. A variety of substituents capable of blocking the metabolism of the electron-rich phenyl ring (R4 or R5 = Cl, F, Br, CH3, OCH3) were well tolerated, affording good to excellent 5-HT2C affinity and increased selectivity over 5-HT2A. 2). These compounds demonstrated low inhibition of CYP1A2 and potent oral activity in the rat.
Radioligands that label 5-HT2C receptors are: [3H]mesulergine (in the presence of a selective 5-HT2A antagonist), [3H]5-HT (with adequate protection with a cocktail of 5-HT1 ligands), [125I]SCH23982 (also dopamine D1), and [125I]LSD (in the presence of adequate 5-HT2A selective drugs). The remarkable concentration of 5-HT2C receptors in the mammalian choroid plexus somehow obscures its presence throughout the CNS. Autoradiographic studies have identified this receptor in anterior olfactory nucleus, olfactory tubercle, lateral amygdaloid nucleus, cortex, nucleus accumbens, hippocampus, amygdala, caudate, and substantia nigra in addition to the choroid plexus in rat brain (Pazos and Palacios 1985).
5-HT2C Receptors in the Pathophysiology of CNS Disease by Jose M. Palacios, Angel Pazos, Daniel Hoyer (auth.), Giuseppe Di Giovanni, Ennio Esposito, Vincenzo Di Matteo (eds.)