The interaction of RS 25259‐197, a potent and selective antagonist, with 5‐HT3 receptors, in vitro

@article{Wong1995TheIO,
  title={The interaction of RS 25259‐197, a potent and selective antagonist, with 5‐HT3 receptors, in vitro},
  author={E. Wong and R. Clark and E. Leung and D. Loury and D. Bonhaus and L. Jakeman and H. Parnes and R. Whiting and R. Eglen},
  journal={British Journal of Pharmacology},
  year={1995},
  volume={114}
}
1 A series of isoquinolines have been identified as 5‐HT3 receptor antagonists. One of these, RS 25259‐197 [(3aS)‐2‐[(S)‐1‐azabicyclo[2.2.2]oct‐3‐yl]‐2,3,3a,4,5,6‐hexahydro‐1‐oxo‐1H‐benzo[de]isoquinoline‐hydrochloride], has two chiral centres. The remaining three enantiomers are denoted as RS 25259‐198 (R,R), RS 25233‐197 (S,R) and RS 25233‐198 (R,S). 2 At 5‐HT3 receptors mediating contraction of guinea‐pig isolated ileum, RS 25259‐197 antagonized contractile responses to 5‐HT in an… Expand
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TLDR
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References

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Pharmacological characterization of RS 25259‐197, a novel and selective 5‐HT3 receptor antagonist, in vivo
TLDR
RS 25259‐197 is a novel, highly potent and orally active 5‐HT3 receptor antagonist in vivo and appears to be a significant improvement over ondansetron in terms of potency and duration of action. Expand
Labelling of 5‐Hydroxytryptamine3 Receptors with a Novel 5‐HT3 Receptor Ligand, [3H]RS‐42358–197
TLDR
Differences in 5‐HT3 receptors of different tissues and species were detected on the basis of statistically significant differences in the affinities of phenylbiguanide, and 1‐(m‐chlorophenyl) biguanide when displacing [3H]RS‐42358‐197 binding. Expand
Pharmacological Characterization of 5‐Hydroxytryptamine3Receptors in Murine Brain and Ileum Using the Novel Radioligand [3H]RS‐42358–197: Evidence for Receptor Heterogeneity
TLDR
5‐HT3 receptors exist as multiple subtypes within species and that subtype‐selective 5‐ HT3 ligands may be identified, and tissue‐and strain‐dependent differences in murine 5-HT3 binding sites are demonstrated. Expand
Characterization of 5‐HT3 and ‘atypical’ 5‐HT receptors mediating guinea‐pig ileal contractions in vitro
TLDR
It is concluded that different 5‐HT receptors mediate excitatory neuronal responses in the guinea‐pig ileal segments, whereas a similar response to 2‐methyl‐5‐HT equalled that obtained with 5‐ HT (second phase). Expand
The pharmacological characterization of 5‐HT3 receptors in three isolated preparations derived from guinea‐pig tissues
TLDR
Comparisons with antagonist affinity values obtained in the rat isolated vagus nerve revealed marked differences, although the differences varied considerably between antagonists. Expand
RS 42358-197, a novel and potent 5-HT3 receptor antagonist, in vitro and in vivo.
TLDR
In dogs, RS 42358-197, administered either intravenously or orally, dose-dependently inhibited the emesis induced by cisplatin, actinomycin and cyclophosphamide, but not that induced by apomorphine, while in rats, this drug was devoid of any agonistic or antagonistic activity at 5-HT1-like receptors. Expand
Identification and Characterisation of 5‐Hydroxytryptamine3 Recognition Sites in Human Brain Tissue
TLDR
It is concluded that [3H]zacopride selectively labels with high affinity 5‐ HT3 recognition sites in human amygdala and hippocampus and, if these binding domains represent 5‐HT3 receptors, may provide the opportunity for 5-HT3 receptor antagonists to modify 5‐ht function in the human brain. Expand
Evidence that the 5‐HT3 receptors of the rat, mouse and guinea‐pig superior cervical ganglion may be different
TLDR
It is concluded that 5‐HT3 receptors are present on the superior cervical ganglion from the rat, mouse and guinea‐pig, but these receptors may be pharmacologically distinct from each other. Expand
Characterization of [3H]Quipazine Binding to 5‐Hydroxytryptamine3 Receptors in Rat Brain Membranes
TLDR
Quipazine was used to label binding sites in rat brain membranes that display characteristics of a 5‐hydroxytryptamine3 (5‐HT3) receptor in the rat CNS and the pharmacological profile of the binding site is in excellent agreement with that of 5-HT3 receptors characterized in peripheral physiological models. Expand
Characteristics of 5‐HT3 binding sites in NG108‐15, NCB‐20 neuroblastoma cells and rat cerebral cortex using [3H]‐quipazine and [3H]‐GR65630 binding
TLDR
In conclusion, [3H]‐quipazine labelled 5‐HT3 receptor sites in homogenates of NG108‐15, NCB‐20 cells and rat cortex (in the presence of 0.1 μm paroxetine) exhibited similar pharmacological characteristics. Expand
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