Tachykinin receptor antagonists in clinical trials

Abstract

Tachykinins (TKs) are small peptides widely distributed in the central and peripheral nervous systems where they act as neurotransmitters. Potent and selective TKs antagonists have been developed in the last 20 years and many efforts have been made to prove their efficacy in the treatment of various diseases. Herein the most prominent results in the clinical development are reported and discussed. For aprepitant, the only compound of this class to have been launched to date, results of clinical studies and postmarketing cost-effectiveness data for the treatment of chemotherapy-induced emesis are discussed. The field is still well active, as currently proof-of-concept studies for indications initially missed (i.e., depression) are ongoing and new targets are under investigation.

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

“…NK2 is additionally found typically in smooth muscles of small and large bronchi and brochioli of human airways. In lung tissues containing membranous airways a fourfold increase in NK2 expression has been described [211] [230]. The NK2 subtype in the brain has been shown by mRNA measurements in caudate putamen, hippocampus, substantia nigra [231].…”

“…substantia nigra, ventral tegmental area and raphe nuclei [208]- [210]. However, it is present in the cerebral regions in low density in comparison with NK1 and NK2 receptors [211].…”

“…A number of non-peptide antagonists at different NK receptor subtypes has been described and achieved in clinical test also phase III [211]. The spectrum of diseases for which such compounds were created was broad and included mental and mood diseases, alcohol craving, overacting bladder, vomiting and also pain syndroms [211].…”

“…The spectrum of diseases for which such compounds were created was broad and included mental and mood diseases, alcohol craving, overacting bladder, vomiting and also pain syndroms [211]. The NK1 receptor has been found to be widely distributed in the brain particularly within the striatum and with negligible density in the cerebellum [212] and relatively early compounds were developed, which could displace [ 3 H]substance P in caudate membranes.…”

“…The indications for the use of NK3 receptors ligands remain restricted to CNS and spinal cord because of the specific presence of this receptor in these regions. A number of clinical studies dedicated to a therapeutic use of NK3 receptor antagonists in schizophrenia, depression and panic disease were discontinued [211].…”