Effect of YM-44781, YM-44778 and YM-49598, Novel Tachykinin Antagonists, in a Drug-Induced Bladder Contraction Model

  title={Effect of YM-44781, YM-44778 and YM-49598, Novel Tachykinin Antagonists, in a Drug-Induced Bladder Contraction Model},
  author={Agnes Choppin and Gretchen Groke and Analyn Bringas and George J Stepan and Michael Patrick Dillon},
  pages={96 - 102}
The radioligand binding profiles and in vivo pharmacological characteristics of YM-44781, YM-44778 and YM-49598, novel non-peptide tachykinin receptor antagonists, were examined and compared to those of FK-888 and GR-159897. Since no functional NK<sub>3</sub> receptors were found in the rat bladder, the emphasis will be on the other two subtypes. YM-44781 and YM-49598 exhibited high binding affinities at NK<sub>2</sub> (pK<sub>i</sub> = 9.94 ± 0.03) and NK<sub>1</sub> (pK<sub>i</sub> = 9.09 ± 0… 

Figures and Tables from this paper

Tachykinin NK2 Receptor Antagonists
These two antagonists combine high affinity for the human tachykinin NK2 receptor with strong antagonist activities in a large variety of in vitro and in vivo pharmacological models and show potent inhibitory activities in visceral nociception suggesting that a tachy Kin2 receptor antagonist may be useful for the treatment of functional gastrointestinal disorders such as irritable bowel syndrome.
Tachykinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Antagonists such as aprepitant and fosaprepitant were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.
Privileged heterocycles: bioactivity and synthesis of 1,9-diazaspiro[5.5]undecane-containing compounds
This review discusses the biological activity and synthesis of 1,9-diazaspiro[5.5]undecanes, including those ring-fused with arenes and heteroarenes and/or containing a carbonyl group at position 2.
Effect of neurokinins on canine prostate cell physiology
This study evaluated the role of neurokinins in proliferation, differentiation, and contraction of canine prostate cells in culture and found that they are important regulators of prostate growth.


Tachykinin NK1 receptor subtypes in the rat urinary bladder
The study investigated the possible heterogeneity of tachykinin NK1 receptors in the rat urinary bladder and found that the idea that a septide‐like receptor may exist in the rats with higher affinity for SP and NKA is compatible with the idea of a ‘novel types’ NK2 receptor blockade.
A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder
The results support the proposal of a mixed population of NK1 and NK2 receptors mediating contraction of the rat isolated urinary bladder.
GR159897, a potent non-peptide antagonist at tachykinin NK2 receptors.
The mammalian tachykinin receptors.
  • C. Maggi
  • Biology, Chemistry
    General pharmacology
  • 1995
MEN 11420 (Nepadutant), a novel glycosylated bicyclic peptide tachykinin NK2 receptor antagonist
The affinities (potency and selectivity) showed by MEN”11420 for different tachykinin receptors, measured either in binding or in functional bioassays, were similar to those shown by the parent compound, MEN’10627.
Spiro-substituted piperidines as neurokinin receptor antagonists. III. Synthesis of (+/-)-N-[2-(3,4-dichlorophenyl)-4-(spiro-substituted piperidin-1'-yl)butyl]-N-methylbenzamides and evaluation of NK1-NK2 dual antagonistic activities.
It is found that a conformation in which the phenyl groups of the N-methylbenzamide and 3,4-dichlorophenyl moieties are close to each other through a cis-amide bond, may be favorable for showing high affinity for the NK1 receptor and that a hydrogen bond-accepting group in the spiro-substituted piperidine moiety may be crucial for exhibiting high affinity in the NK2 receptor.
Highly selective agonists for substance P receptor subtypes.
The action of selective SP‐N agonists in the guinea pig ileum is antagonized by opioid peptides, suggesting a functional counteraction between opiate andSP‐N receptors, indicating that the tachykinin receptors are distinct entities which may mediate different physiological functions.