By Robin D. Clark (auth.), Richard M. Eglen Ph.D. (eds.)
This ebook presents a accomplished, up to date evaluation of the distribution, pharmacology and body structure of crucial 5-hydroxytryptamine (5-HT)4 receptors. The 5-HT receptor subtypes express a different pharmacology, distribution and serve as, of which the 5-HT4 receptor has been some of the most intensively studied lately, either from a easy study point of view and as a objective for novel therapeutics.
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Additional info for 5-HT4 Receptors in the Brain and Periphery
Br J Pharmacol1994; 113:12oP. 73· Gale JD, Green A, Darton J et al. GR125487: a 5-HT4 receptor antagonist with a long duration of action in vivo. Br J Pharmacol1994; 113:119P. 74· King DF, Gaster LM, Mulholland KR. 5-HT4 receptor antagonists. lnt Pat Appl1994; WO 94/27987. 75· Parker SG, HamburgerS, Taylor EM et al. SB203186, a potent 5-HT4 receptor antagonist, in porcine sinoatrial and human and porcine atriuim. Br J Pharmacol1993; 1o8:68P. 76. Wyman PA, Gaster LM, King FD et al. Azabicyclo indole esters as potent 5-HT4 receptor antagonists.
0 aReference 70. bAntagonism of 5-HT induced relaxation of rat, carbachol contracted esophagus muscularis mucosae. cpartial agonist. 12. SAR o/2-benzyloxyaryl ketone S-HT4 receptor antagonists a 0 Cl~ u,N I-"' ~x N,R ~ X pKt,C pK;b compd. 3 •Reference 70. bDisplacement of [3H]GR 113808 from guinea-pig striatal membranes. CAntagonism of 5-HT mediated relaxation of rat, carbachol contracted esophageal muscularis mucosae. 13. SAR of benzodioxanyl ketone 5-HT4 receptor antagonists a 0 compd. 0 "Reference 71.
So s-HT4 Receptors in the Brain and Periphery activation via the stimulation of cAMP production. The 5- HT 4 receptor is a member of this cyclase stimulatory serotonin receptor set. 12' 22 Both s-HT640 and 5-HT7 receptors 7•34•44 A7>48 are also coupled to stimulation of adenylate cyclase. Although one of the early subtypes to be characterized pharmacologically, the 5- HT 4 receptor was the last to be cloned. Cloning of the Rat 5-HT4 Receptor In order to clone the s-HT 4 receptor, rat brain eDNA was used as a template for PCR amplification with two degenerate oligonucleotide primers derived from the third and fifth transmembrane (TM) domains which are highly conserved in serotonin receptors.
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