BRL 46470A: a highly potent, selective and long acting 5-HT3 receptor antagonist with anxiolytic-like properties

@article{Blackburn1993BRL4A,
  title={BRL 46470A: a highly potent, selective and long acting 5-HT3 receptor antagonist with anxiolytic-like properties},
  author={Thomas P Blackburn and Gordon Smith Baxter and Guy A. Kennett and Frank D. King and David C. Piper and Graham J Sanger and D. R. Thomas and Neil Upton and Martyn D. Wood},
  journal={Psychopharmacology},
  year={1993},
  volume={110},
  pages={257-264}
}
The novel 5-HT3 antagonist, BRL 46470A (endo-N-(8-methyl-8-azabicyclo [3.2.1]oct-3-yl)2,3-dihydro-3,3 dimethyl-indole-1-carboxamide, hydrochloride), has been investigated in a series of in vitro and in vivo tests, including the effect of the drug in models of anxiolysis. In classical tests for 5-HT3 receptor antagonism, BRL 46470A was shown to antagonise 5-HT3 mediated responses in the guinea-pig ileum [pA2 8.3±0.5, slope 0.98±0.20, mean±SEM (5)], the rabbit isolated heart (pA2 10.1±0.1, slope… 

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References

SHOWING 1-10 OF 44 REFERENCES

MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors

  • J. Fozard
  • Biology
    Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2004
MDL 72222 is the first reported selective and potent antagonist of responses mediated through the 5-HT receptors present on the terminal sympathetic neurones of the rabbit heart and on the neurones subserving the afferent limb of the Bezold-Jarisch reflex.

Characterization of the binding of [3H]L-365,260: a new potent and selective brain cholecystokinin (CCK-B) and gastrin receptor antagonist radioligand.

The data indicates that [3H]L-365,260 represents a new potent nonpeptide antagonist radioligand suitable for the study of brain CCK-B and gastrin receptors.

Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding

Direct evidence for the existence of 5-HT3 receptors in rat brain tissue and their distribution is reported, based on high affinity binding of the potent 5- HT3 receptor antagonist 3H-GR65630 to homogenates of rat entorhinal cortex.

5-Methoxytryptamine and 2-methyl-5-hydroxytryptamine-induced desensitization as a discriminative tool for the 5-HT3 and putative 5-HT4 receptors in guinea pig ileum

It is concluded that 5-methoxytryptamine and 2-methyl-5-HT can be utilized as selective probes to discriminate the putative 5-HT4 receptor from the 5- HT3 receptor in guinea pig ileum.

5-HT1D receptors in guinea-pig and pigeon brain

It is suggested that 5-HT1D sites may be present in the brain of the majority of vertebrate species located higher than the sauropside-mammalian divergence in the phylogenic tree, whereas 5- HT1B sites are only found in some rodents.

Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists.

Characterization of the binding of [3H]-(+/-)-L-364,718: a new potent, nonpeptide cholecystokinin antagonist radioligand selective for peripheral receptors.

Data indicate that [3H]-(+/-)-L-364,718 represents a new potent nonpeptide antagonist radioligand for the study of peripheral CCK receptors which may allow differentiation of agonist and antagonist interactions.

5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae

Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, sugesting that 5- HT-induced relaxation of the tunica muscularis mucosae was mediated via a postjunctional receptor, independent of endogenous prostanoids.