Although the 5-HT(5) receptor subfamily was discovered more than
15 years ago, it is unambiguously the least known 5-HT receptor
subtype. The G(i)/G(0)-mediated signal transduction and its
intensive presence in raphe and other brainstem and pons nuclei
suggest mechanisms similar to those of 5-HT(1) receptors, the
ligands of which are already applied in the treatment of e.g.
anxiety and migraine. In addition, a unique coupling and
inhibition of adenosine diphosphate-ribosyl cyclase have also
been described. High concentrations of 5-HT(5) receptor in other
key regions including, e.g. locus coeruleus, nucleus of the
solitary tract, arcuate and suprachiasmatic nuclei of the
hypothalamus indicate a wide range of physiological effects,
thus its ligands are potential drug candidates in various
areas, e.g. anxiety, sleep, incontinence, food intake, learning
and memory, pain or chemoreception pathways. These findings
have motivated several institutes and pharmaceutical companies
to participate in the research of this field. Despite extensive
research, no selective agonist and only two selective
antagonists have been identified until now. Beyond these
compounds, the present review provides a complete overview on
all other published 5-HT(5A) receptor ligands as well as on the
structure, function, distribution, genetics and possible
therapeutic applications of this receptor.
