5-HT4 Receptors in the Brain and Periphery by Robin D. Clark (auth.), Richard M. Eglen Ph.D. (eds.)

By Robin D. Clark (auth.), Richard M. Eglen Ph.D. (eds.)

This booklet presents a entire, up to date assessment of the distribution, pharmacology and body structure of valuable 5-hydroxytryptamine (5-HT)4 receptors. The 5-HT receptor subtypes express a special pharmacology, distribution and serve as, of which the 5-HT4 receptor has been some of the most intensively studied in recent times, either from a simple study perspective and as a goal for novel therapeutics.

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5-HT4 receptor antagonism by SB 204070 inhibits 5-hydroxytryptophan-evoked defaecation in mice. Br J Pharmacol1993; 110:17P. 20. Hegde SS, Moy TM, Perry M et al. Evidence for the involvement of 5-HT4 receptors in 5- hydroxytryptophan-induced diarrhea in mice. J Pharmacol Exp Ther 1994; 271:741-747. 21. Villalon CM, Den Boer MO, Heligers JP et al. Further characterization, by the use of tryptamine and benzamide derivatives, of the putative 5-HT 4 receptor mediating tachycardia in the pig. Br J Pharmacol 1991; 102:107-112.

83 84(VB20B7) 91 [ 1251]SB 207710 92 (SC -53606) 93 s-HT4 Receptors in the Brain and Periphery 24 cixXu 0 0 I HzN h Cl~ ~N~ N ~OMc ~NHSOzMe y H,Ny? 0~ -? ~I 96 (RS-100235) OMe OMc 95 (RS-39604) 10 (GR 113808) 122 (GR 125487) 123 (SB 203186) c3 l">6 0 ~ N ' Me 135 (SC-56184) 134 143 (SB 207266) o3 J'"'>6 0 N N ' Me 147 148 Me N. 5. 6. 5. 1. 5-HT4 Receptor Activity for Piperidinoethyl Benzoatesa Clxi,~O I 0 H2N A R compd. 8 inactive 100 •Reference 36. "Displacement of eHJGR 113808 from rat striatal membranes.

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. Bioor Med Chern 1996; 4:255-261. 77· Gaster LM, Joiner GF, King FD et al. N-((1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H- [1,3]oxazino[3,2-a]indole-1o-carboxamide hydrochloride: The first potent and selective 5- HT4 receptor antagonist amide with oral activity.

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