Recent progress in 5-HT₇receptors: potential treatment of central and peripheral nervous system diseases

Abstract

In light of the barrage of recent reviews on 5-HT 7 receptor agonists and antagonists, this article will highlight and review the research advances published in the patent literature between January 1997 and December 2003. The article is supplemented with selected references on the design, synthesis and development of novel 5-HT 7 agents to treat central and peripheral nervous system diseases. Emphasis is placed on recent advances in the possible involvement of 5-HT 7 serotonergic agents in the treatment of learning and memory, depression, schizophrenia and migraine. By no means has any attempt been made to exhaustively review the literature, but rather, primary references together with citations to recent literature reviews have been included in each section.

Structure of the human 5-HT7 receptor gene and characterization of its promoter region

“…The recent development of 5-HT 7 receptor-selective antagonists and the generation of a 5-HT 7 knock-out mouse (Hedlund et al, 2003) have accelerated the investigation of the role of the 5-HT 7 receptor in brain function. Evidence is increasing which suggests a role for the 5-HT 7 receptor in the control of circadian rhythms and sleep (Lovenberg et al, 1993;Thomas et al, 2003;Slassi et al, 2004;Sprouse et al, 2004;Thomas and Hagan, 2004). In correlation herewith is the postulated role for the 5-HT 7 receptor in depression.…”

5-HT7 Receptor Ligands: Recent Developments and Potential Therapeutic Applications

“…Subsequently a number of pharmaceutical companies and academic research groups reported the identification of selective 5-HT 7 R ligands and excellent reviews in the field were provided during 2004 [62,64]. Briefly, some of the most interesting ligands worth of mention are: tetrahydroquinolines from Roche, aporphine derivatives from Uppsala University, aminoalkylpirrolidines and amidinoureas from Pfizer, 6-bromo-1-substituted-ethylindoles from NPS Pharmaceuticals, carbocyclic sulfonamide derivatives and dimethyl-(2-arylsulfanylethyl)amines from Merck & Co. Inc. [93][94][95][96][97][98][99][100][101].…”

“…The pharmacological aspects of 5-HT 7 Rs have been reviewed in 2004 [62,63,65,66]. Initial progresses in the elucidation of potential therapeutic function of 5-HT 7 Rs have been made using unselective ligands in the presence of masking agents.…”

“…The characterization and distribution of 5-HT 7 Rs along with their ligands have been reviewed up to 2004 [57][58][59][60][61][62][63][64][65][66]. The aim of this review is to discuss the literature concerning recent advances on 5-HT 7 Rs, from a medicinal chemistry perspective.…”